|
1
|
Tavassoli N, Ghahremani A, Namakin K, Naserghandi A, Miri SR, Abdolahad M. Intra Operative Mild Cooling of Large Tumors Reduces Their Invasive and Metastatic Functions While Increasing Their Resistance to Apoptosis. Ther Hypothermia Temp Manag 2024; 14:290-298. [PMID: 38079194 PMCID: PMC11665270 DOI: 10.1089/ther.2023.0060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2024] Open
Abstract
Cancer treatment often involves excisional surgery, but this approach may leave behind minimal residual disease, leading to tumor regrowth. Proinflammatory cytokines and their role in altering residual cancerous cells postsurgery have garnered attention. The study examines how mild intraoperative cooling affects cancer cells and their gene expression. It aims to discover strategies for reducing tumor growth after surgery. Nine cases of solid tumor were included in the study, nine samples were cooled with the Peltier-Seebeck device down to12°C, and cooled and noncooled regions of tumors were analyzed using reverse transcription-polymerase chain reaction. Key transcriptomes, including neural-cadherin, cadherins (CDH), 70-kDa Heat Shock Protein (HSP70), hypoxia-inducible factor (HIF), Y-Box-binding protein 1 (YB-1), matrix metalloproteinase 9 (MMP9), and matrix metalloproteinase 2 (MMP2), were measured to assess the impact of mild hypothermia on cancer cell metabolism and cold shock responses. Analysis of cooled and noncooled regions revealed reduced MMP2/9 levels in cooled regions in five out of seven cases, indicating potential suppression of tumor invasion and metastasis. CDH-1 expression was detected in five cases, with decreased levels observed in cooled regions in most cases, suggesting a role in tumor aggressiveness. YB-1 expression was increased in six out of eight samples, possibly correlating with local recurrence and reduced overall survival times. N-Cad expression was increased in all five samples where it was detected, indicating its potential involvement in tumor cell motility and invasion. HSPs showed a mild increase in four out of five cases following cooling, potentially contributing to tumor cell resistance to cooling-induced apoptosis. Intraoperative mild cooling resulted in the downregulation of key proteins playing a role in invasion and metastasis. However, Elevated YB-1 and N-Cad expression limits cooling's universal application. Further research is necessary to comprehend cooling-related transcriptome changes and their impact on patient outcomes.
Collapse
Affiliation(s)
- Noureddin Tavassoli
- Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Ghahremani
- Nano Bio Electronic Devices Lab, Nano Electronic Center of Excellence, School of Electrical and Computer Engineering, College of Engineering, University of Tehran, Tehran, Iran
| | - Kosar Namakin
- Nano Bio Electronic Devices Lab, Nano Electronic Center of Excellence, School of Electrical and Computer Engineering, College of Engineering, University of Tehran, Tehran, Iran
- Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Alvand Naserghandi
- Nano Bio Electronic Devices Lab, Nano Electronic Center of Excellence, School of Electrical and Computer Engineering, College of Engineering, University of Tehran, Tehran, Iran
- Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Rouhollah Miri
- Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Abdolahad
- Nano Bio Electronic Devices Lab, Nano Electronic Center of Excellence, School of Electrical and Computer Engineering, College of Engineering, University of Tehran, Tehran, Iran
| |
Collapse
|
|
2
|
Teng Z, Wang S, Yuan H, Wang H, Li J, Chang X, Zhang Y, Han Z, Wang Y. MMP-9 gene polymorphisms on cancer risk: an updated systematic review and meta-analysis. NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS 2024; 43:1090-1113. [PMID: 38166515 DOI: 10.1080/15257770.2023.2299710] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 10/05/2023] [Accepted: 12/04/2023] [Indexed: 01/04/2024]
Abstract
To provide a comprehensive account of the association of MMP-9 gene polymorphisms (rs3918242) with susceptibility to cancer. A literature search for eligible candidate gene studies published before May 27, 2022 was conducted in PubMed, Medline, Google Scholar and Web of Science. Potential sources of heterogeneity were sought out across subgroups and sensitivity analysis. Publication bias were also estimated. Overall, a total of 37 articles with 7616 cases and 8165 controls for rs3918242 gene polymorphisms were enrolled. Our meta-analysis suggests that MMP-9 rs3918242 might be associated with breast cancer and gastric cancer susceptibility, and perhaps reduce the risk of lung cancer.
Collapse
Affiliation(s)
- Zhihai Teng
- Department of Urology, the Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Song Wang
- Department of Urology, the Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Hao Yuan
- Department of Urology, the Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Hu Wang
- Department of Urology, the Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Jingdong Li
- Department of Urology, the Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xueliang Chang
- Department of Urology, the Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yanping Zhang
- Department of Urology, the Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Zhenwei Han
- Department of Urology, the Second Hospital of Hebei Medical University, Shijiazhuang, China
| | - Yaxuan Wang
- Department of Urology, the Second Hospital of Hebei Medical University, Shijiazhuang, China
| |
Collapse
|
|
3
|
Sokolova O, Naumann M. Matrix Metalloproteinases in Helicobacter pylori-Associated Gastritis and Gastric Cancer. Int J Mol Sci 2022; 23:1883. [PMID: 35163805 PMCID: PMC8836485 DOI: 10.3390/ijms23031883] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 02/02/2022] [Accepted: 02/04/2022] [Indexed: 02/05/2023] Open
Abstract
Gastric cancer is one of the leading causes of the cancer-related mortality worldwide. The etiology of this disease is complex and involves genetic predisposition and environmental factors, including Helicobacter pylori. Infection of the stomach with H. pylori leads to gastritis and gastric atrophy, which can progress stepwise to gastric cancer. Matrix metalloproteinases (MMPs) actively participate in the pathology development. The further progression of gastric cancer seems to be less dependent on bacteria but of intra-tumor cell dynamics. Bioinformatics data confirmed an important role of the extracellular matrix constituents and specific MMPs in stomach carcinoma invasion and metastasis, and revised their potential as predictors of the disease outcome. In this review, we describe, in detail, the impact of MMPs in H. pylori-associated gastritis and gastric cancer.
Collapse
Affiliation(s)
- Olga Sokolova
- Institute of Experimental Internal Medicine, Medical Faculty, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany
| | - Michael Naumann
- Institute of Experimental Internal Medicine, Medical Faculty, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany
| |
Collapse
|
|
4
|
Proteomic Signatures of Diffuse and Intestinal Subtypes of Gastric Cancer. Cancers (Basel) 2021; 13:cancers13235930. [PMID: 34885041 PMCID: PMC8656738 DOI: 10.3390/cancers13235930] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2021] [Revised: 11/20/2021] [Accepted: 11/23/2021] [Indexed: 12/14/2022] Open
Abstract
Gastric cancer is a leading cause of death from cancer globally. Gastric cancer is classified into intestinal, diffuse and indeterminate subtypes based on histology according to the Laurén classification. The intestinal and diffuse subtypes, although different in histology, demographics and outcomes, are still treated in the same fashion. This study was designed to discover proteomic signatures of diffuse and intestinal subtypes. Mass spectrometry-based proteomics using tandem mass tags (TMT)-based multiplexed analysis was used to identify proteins in tumor tissues from patients with diffuse or intestinal gastric cancer with adjacent normal tissue control. A total of 7448 or 4846 proteins were identified from intestinal or diffuse subtype, respectively. This quantitative mass spectrometric analysis defined a proteomic signature of differential expression across the two subtypes, which included gremlin1 (GREM1), bcl-2-associated athanogene 2 (BAG2), olfactomedin 4 (OLFM4), thyroid hormone receptor interacting protein 6 (TRIP6) and melanoma-associated antigen 9 (MAGE-A9) proteins. Although GREM1, BAG2, OLFM4, TRIP6 and MAGE-A9 have all been previously implicated in tumor progression and metastasis, they have not been linked to intestinal or diffuse subtypes of gastric cancer. Using immunohistochemical labelling of a tissue microarray comprising of 124 cases of gastric cancer, we validated the proteomic signature obtained by mass spectrometry in the discovery cohort. Our findings should help investigate the pathogenesis of these gastric cancer subtypes and potentially lead to strategies for early diagnosis and treatment.
Collapse
|
|
5
|
Circulating Biomarkers of Colorectal Cancer (CRC)-Their Utility in Diagnosis and Prognosis. J Clin Med 2021; 10:jcm10112391. [PMID: 34071492 PMCID: PMC8199026 DOI: 10.3390/jcm10112391] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2021] [Revised: 05/25/2021] [Accepted: 05/25/2021] [Indexed: 02/06/2023] Open
Abstract
The global burden of colorectal cancer (CRC) is expected to increase, with 2.2 million new cases and 1.1 million annual deaths by 2030. Therefore, the establishment of novel biomarkers useful in the early diagnosis of CRC is of utmost importance. A number of publications have documented the significance of the overexpression of several specific proteins, such as inflammatory mediators, in CRC progression. However, little is known about the potential utility of these proteins as circulating blood tumor biomarkers of CRC. Therefore, in the present review we report the results of our previous original studies as well as the findings of other authors who investigated whether inflammatory mediators might be used as novel biomarkers in the diagnosis and prognosis of CRC. Our study revealed that among all of the tested proteins, serum M-CSF, CXCL-8, IL-6 and TIMP-1 have the greatest value in the diagnosis and progression of CRC. Serum TIMP-1 is useful in differentiating between CRC and colorectal adenomas, whereas M-CSF and CRP are independent prognostic factors for the survival of patients with CRC. This review confirms the promising significance of these proteins as circulating biomarkers for CRC. However, due to their non-specific nature, further validation of their sensitivity and specificity is required.
Collapse
|
|
6
|
Gallyamova LF, Nurgalieva AK, Khidiyatov II, Nasibullin TR, Munasypov FR, Khusnutdinov SM, Rakhimov RR, Abdeev RR, Sakaeva DD, Khusnutdinova EK. The Role of Polymorphic Variants of Several Genes of Matrix Metalloproteinases and Their Tissue Inhibitors in the Development of Gastric Cancer. RUSS J GENET+ 2021. [DOI: 10.1134/s1022795421050021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
|
|
7
|
Cabral-Pacheco GA, Garza-Veloz I, Castruita-De la Rosa C, Ramirez-Acuña JM, Perez-Romero BA, Guerrero-Rodriguez JF, Martinez-Avila N, Martinez-Fierro ML. The Roles of Matrix Metalloproteinases and Their Inhibitors in Human Diseases. Int J Mol Sci 2020; 21:E9739. [PMID: 33419373 PMCID: PMC7767220 DOI: 10.3390/ijms21249739] [Citation(s) in RCA: 854] [Impact Index Per Article: 170.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Revised: 12/10/2020] [Accepted: 12/18/2020] [Indexed: 02/07/2023] Open
Abstract
Matrix metalloproteinases (MMPs) are a family of zinc-dependent extracellular matrix (ECM) remodeling endopeptidases that have the capacity to degrade almost every component of the ECM. The degradation of the ECM is of great importance, since it is related to embryonic development and angiogenesis. It is also involved in cell repair and the remodeling of tissues. When the expression of MMPs is altered, it can generate the abnormal degradation of the ECM. This is the initial cause of the development of chronic degenerative diseases and vascular complications generated by diabetes. In addition, this process has an association with neurodegeneration and cancer progression. Within the ECM, the tissue inhibitors of MMPs (TIMPs) inhibit the proteolytic activity of MMPs. TIMPs are important regulators of ECM turnover, tissue remodeling, and cellular behavior. Therefore, TIMPs (similar to MMPs) modulate angiogenesis, cell proliferation, and apoptosis. An interruption in the balance between MMPs and TIMPs has been implicated in the pathophysiology and progression of several diseases. This review focuses on the participation of both MMPs (e.g., MMP-2 and MMP-9) and TIMPs (e.g., TIMP-1 and TIMP-3) in physiological processes and on how their abnormal regulation is associated with human diseases. The inclusion of current strategies and mechanisms of MMP inhibition in the development of new therapies targeting MMPs was also considered.
Collapse
Affiliation(s)
| | - Idalia Garza-Veloz
- Molecular Medicine Laboratory, Unidad Académica de Medicina Humana y Ciencias de la Salud, Carretera Zacatecas-Guadalajara Km.6. Ejido la Escondida, Zacatecas 98160, Mexico; (G.AC.-P.); (C.C.-D.l.R.); (J.MR.-A.); (B.AP.-R.); (J.FG.-R.); (N.M.-A.)
| | | | | | | | | | | | - Margarita L Martinez-Fierro
- Molecular Medicine Laboratory, Unidad Académica de Medicina Humana y Ciencias de la Salud, Carretera Zacatecas-Guadalajara Km.6. Ejido la Escondida, Zacatecas 98160, Mexico; (G.AC.-P.); (C.C.-D.l.R.); (J.MR.-A.); (B.AP.-R.); (J.FG.-R.); (N.M.-A.)
| |
Collapse
|
|
8
|
Tai J, Sun D, Wang X, Kang Z. Matrix metalloproteinase-8 rs11225395 polymorphism correlates with colorectal cancer risk and survival in a Chinese Han population: a case-control study. Aging (Albany NY) 2020; 12:19618-19627. [PMID: 33052136 PMCID: PMC7732324 DOI: 10.18632/aging.103930] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Accepted: 08/01/2020] [Indexed: 01/24/2023]
Abstract
Matrix metalloproteinase-8 (MMP-8) is a gene associated with inflammation and prognosis in colorectal cancer (CRC). Here, we studied the link between the rs11225395 polymorphism of MMP-8 gene and CRC risk. We recruited 551 CRC cases and 623 controls from among a subpopulation of Han Chinese patients. Data found that this variant was connected to an increased risk of CRC (TT versus CC: OR, 1.76; 95%CI, 1.09-2.84; P = 0.021; T versus C: OR, 1.29; 95%CI, 1.07-1.56; P = 0.007). Stratified analyses indicated a positive association among smokers (TT versus CC: OR, 2.31; 95%CI, 1.12-4.79; P = 0.024), males, and patients ≥ 60 years old. Crossover analysis showed that the potential interaction between smoking or drinking and the MMP-8 rs11225395 polymorphism was related to elevated risk for CRC. The rs11225395 polymorphism was also connected with lymph node metastasis and TNM stage. Moreover, the CRC cases carrying a TT genotype of MMP-8 rs11225395 presented had poorer overall survival than the CC genotype carriers. These findings show that MMP-8 rs11225395 correlates with an elevated risk of CRC and poor patient prognosis in a subpopulation of the Han Chinese subpopulation. Thus, the MMP-8 rs11225395 polymorphism could potentially function as a biomarker predictive of CRC susceptibility.
Collapse
Affiliation(s)
- Jiandong Tai
- Department of Colorectal and Anal Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin, China
| | - Di Sun
- Department of Colorectal and Anal Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin, China
| | - Xu Wang
- Department of Colorectal and Anal Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin, China
| | - Zhenhua Kang
- Department of Colorectal and Anal Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin, China
| |
Collapse
|
|
9
|
Zare M, Jafari-Nedooshan J, Aghili K, Ahrar H, Jarahzadeh MH, Seifi-Shalamzari N, Zare-Shehneh M, Neamatzadeh H. ASSOCIATION OF MMP-7 -181A>G POLYMORPHISM WITH COLORECTAL CANCER AND GASTRIC CANCER SUSCEPTIBILITY: A SYSTEMATIC REVIEW AND META-ANALYSIS. ACTA ACUST UNITED AC 2019; 32:e1449. [PMID: 31644669 PMCID: PMC6812146 DOI: 10.1590/0102-672020190001e1449] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Accepted: 01/16/2019] [Indexed: 02/06/2023]
Abstract
Introduction:
The matrix metalloproteinase-7 (MMP-7) gene -181A>G polymorphism has been
reported to be associated with colorectal cancer (CRC) and gastric cancer
(GC) susceptibility, yet the results of these previous results have been
inconsistent or controversial.
Aim:
To elaborate a meta-analysis to assess the association of -181A>G
polymorphism of MMP-7 with CRC and GC risk.
Methods:
Published literature evaluating the association from PubMed, Web of Science,
Google Scholar and other databases were retrieved up to April 25, 2018.
Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated
using random- or fixed-effects model.
Results:
A total of 19 case-control studies, which included eleven studies on CRC
(2,169 CRC cases and 2,346 controls) and eight studies on GC (1,545 GC cases
and 2,366 controls) were identified. There was a significant association
between MMP-7 -181A>G polymorphism and GC risk under the homozygote model
(GG vs. AA: OR=1.672, 95% CI 1.161-2.409, p=0.006) and the recessive model
(GG vs. GA+AA: OR=1.672, 95% CI 1.319-2.554, p=0.001), but not with CRC. By
subgroup analysis based on ethnicity, an increased risk of CRC and GC was
found only among Asians.
Conclusions:
This meta-analysis suggests that MMP-7 -181A>G polymorphisms is associated
with GC risk, but not with CRC. However, our results clearly showed that the
MMP-7 -181A>G polymorphism significantly increased the risk of CRC only
in Asians.
Collapse
Affiliation(s)
- Mohammad Zare
- Shahid Sadoughi University of Medical Sciences, General Surgery
| | | | - Kazem Aghili
- Shahid Sadoughi University of Medical Sciences, Radiology
| | - Hossein Ahrar
- Shahid Sadoughi University of Medical Sciences, Radiology
| | | | | | | | | |
Collapse
|
|
10
|
Feng J, Chen Y, Hua W, Sun X, Chen Y, Liu Y, Fan J, Zhao Y, Zhao L, Xu X, Yang X. The MMP -8 rs11225395 Promoter Polymorphism Increases Cancer Risk of Non-Asian Populations: Evidence from a Meta-Analysis. Biomolecules 2019; 9:E570. [PMID: 31590330 PMCID: PMC6843622 DOI: 10.3390/biom9100570] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2019] [Revised: 09/30/2019] [Accepted: 10/02/2019] [Indexed: 12/11/2022] Open
Abstract
This meta-analysis aimed to systematically review the evidence on cancer risk of the MMP-8 rs11225395 promoter polymorphism. Relevant studies published by 12 June 2019 were identified by systematically searching PubMed, Web of Science, Cochrane Library, CNKI and Wanfang databases. R programs and STATA software were used to calculate odds ratio (OR) and 95% confidence interval (CI). In total, 7375 cancer samples and 8117 controls were included by integrating 15 case-control data sets. Pooled estimates from the statistical analysis revealed no statistical significance for the association between this polymorphism and cancer risk. All pooled estimates resulting from subgroup analyses by cancer type and sample size were not materially altered and did not draw significantly different conclusions. The stratified analyses according to geographic region showed the statistical significance for increased cancer risk of the MMP-8 rs11225395 polymorphism in non-Asian populations under the allele model (OR = 1.11, 95% CI: 1.04-1.19), homozygote model (OR = 1.22, 95% CI: 1.05-1.41), heterozygote model (OR = 1.21, 95% CI: 1.07-1.36), and dominant model (OR = 1.21, 95% CI: 1.08-1.35). However, no statistical significance was detected in Asian populations. In conclusion, these findings suggested that the MMP-8 rs11225395 polymorphism is associated with elevated susceptibility to cancer in non-Asian populations.
Collapse
Affiliation(s)
- Jiarong Feng
- Department of Bioinformatics, School of Biology and Basic Medical Sciences, Soochow University, 199 Ren’ai Road, Suzhou 215123, China (Y.C.); (X.S.); (Y.C.)
| | - Yudi Chen
- Department of Bioinformatics, School of Biology and Basic Medical Sciences, Soochow University, 199 Ren’ai Road, Suzhou 215123, China (Y.C.); (X.S.); (Y.C.)
| | - Wenxi Hua
- Medical College, Soochow University, 199 Ren’ai Road, Suzhou 215123, China (Y.Z.)
| | - Xiaohan Sun
- Department of Bioinformatics, School of Biology and Basic Medical Sciences, Soochow University, 199 Ren’ai Road, Suzhou 215123, China (Y.C.); (X.S.); (Y.C.)
| | - Yanjie Chen
- Department of Bioinformatics, School of Biology and Basic Medical Sciences, Soochow University, 199 Ren’ai Road, Suzhou 215123, China (Y.C.); (X.S.); (Y.C.)
| | - Yu Liu
- Department of Bioinformatics, School of Biology and Basic Medical Sciences, Soochow University, 199 Ren’ai Road, Suzhou 215123, China (Y.C.); (X.S.); (Y.C.)
| | - Jiaying Fan
- Department of Biotechnology, School of Biology and Basic Medical Sciences, Soochow University, 199 Ren’ai Road, Suzhou 215123, China;
| | - Yuening Zhao
- Medical College, Soochow University, 199 Ren’ai Road, Suzhou 215123, China (Y.Z.)
| | - Lixiang Zhao
- Department of Immunology, School of Biology and Basic Medical Sciences, Soochow University, 199 Ren’ai Road, Suzhou 215123, China
| | - Xiaojing Xu
- Department of Cell Biology, School of Biology and Basic Medical Sciences, Soochow University, 199 Ren’ai Road, Suzhou 215123, China
| | - Xiaoqin Yang
- Department of Bioinformatics, School of Biology and Basic Medical Sciences, Soochow University, 199 Ren’ai Road, Suzhou 215123, China (Y.C.); (X.S.); (Y.C.)
| |
Collapse
|
|
11
|
The Role of MMP8 in Cancer: A Systematic Review. Int J Mol Sci 2019; 20:ijms20184506. [PMID: 31514474 PMCID: PMC6770849 DOI: 10.3390/ijms20184506] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Revised: 09/06/2019] [Accepted: 09/08/2019] [Indexed: 12/24/2022] Open
Abstract
Matrix metalloproteinases (MMPs) have traditionally been considered as tumor promoting enzymes as they degrade extracellular matrix components, thus increasing the invasion of cancer cells. It has become evident, however, that MMPs can also cleave and alter the function of various non-matrix bioactive molecules, leading to both tumor promoting and suppressive effects. We applied systematic review guidelines to study MMP8 in cancer including the use of MMP8 as a prognostic factor or as a target/anti-target in cancer treatment, and its molecular mechanisms. A total of 171 articles met the inclusion criteria. The collective evidence reveals that in breast, skin and oral tongue cancer, MMP8 inhibits cancer cell invasion and proliferation, and protects patients from metastasis via cleavage of non-structural substrates. Conversely, in liver and gastric cancers, high levels of MMP8 worsen the prognosis. Expression and genetic alterations of MMP8 can be used as a prognostic factor by examination of the tumor and serum/plasma. We conclude, that MMP8 has differing effects on cancers depending on their tissue of origin. The use of MMP8 as a prognostic factor alone, or with other factors, seems to have potential. The molecular mechanisms of MMP8 in cancer further emphasize its role as an important regulator of bioactive molecules.
Collapse
|
|
12
|
Tafrihi M, Golbabaei M, Shokrzadeh M. Association of the −181 G→A polymorphism in the MMP-7 gene promoter and gastric cancer: A case-control study. Meta Gene 2019. [DOI: 10.1016/j.mgene.2019.100594] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
|
|
13
|
Yuan HF, Li Y, Ye WH, Liu Y, Zhang ZD, Tan BB, Fan LQ, Zhao Q, Wang D, Jia N, Hao YJ. Downregulation of annexin A7 decreases proliferation, migration, and invasion of gastric cancer cells by reducing matrix metalloproteinase 1 and 9 expression. Am J Transl Res 2019; 11:2754-2764. [PMID: 31217851 PMCID: PMC6556647] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2019] [Accepted: 05/01/2019] [Indexed: 06/09/2023]
Abstract
High annexin A7 expression is a potential indicator of lymphatic metastasis and poor prognosis in patients with gastric cancer (GC). The mechanism underlying the effects of annexin A7 on GC cells remains unclear. In patients with GC, primary adenocarcinoma tissues had higher annexin A7 expression than adjacent non-cancerous tissues (P < 0.05). Among three human GC cell lines with high, moderate, and low levels of differentiation, respectively, the cell line with the lowest level of differentiation displayed the highest level of annexin A7 expression. We transfected cells of the human GC cell line BGC823 with short interfering RNAs (siRNAs) targeting annexin A7 and investigated the effects on signaling pathways related to cancer progression by quantitative real-time PCR and western blot. The silencing of endogenous annexin A7 suppressed the proliferation, migration, and invasion abilities of the BGC823 cells. In the cells treated with annexin A7 siRNA, the expression of p16, p21, and p27 was significantly upregulated while that of proliferating cell nuclear antigen (PCNA), cyclin A, cyclin D1, cyclin E1, matrix metalloproteinase-2 (MMP-2), MMP-9, and intercellular cell-adhesion molecule-1 (ICAM-1) was significantly downregulated compared with that in control cells. Our results suggest that the downregulation of endogenous annexin A7 inhibits GC cell proliferation, migration, and invasion by impacting cell cycle regulators and the expression of MMP-1, MMP-2, and ICAM-1. Targeting annexin A7 may represent a valuable strategy for the diagnosis and clinical treatment of GC.
Collapse
Affiliation(s)
- Hu-Fang Yuan
- The Third Department of Surgery, The Fourth Hospital of Hebei Medical University Shijiazhuang 050011, China
| | - Yong Li
- The Third Department of Surgery, The Fourth Hospital of Hebei Medical University Shijiazhuang 050011, China
| | - Wei-Hua Ye
- The Third Department of Surgery, The Fourth Hospital of Hebei Medical University Shijiazhuang 050011, China
| | - Yu Liu
- The Third Department of Surgery, The Fourth Hospital of Hebei Medical University Shijiazhuang 050011, China
| | - Zhi-Dong Zhang
- The Third Department of Surgery, The Fourth Hospital of Hebei Medical University Shijiazhuang 050011, China
| | - Bi-Bo Tan
- The Third Department of Surgery, The Fourth Hospital of Hebei Medical University Shijiazhuang 050011, China
| | - Li-Qiao Fan
- The Third Department of Surgery, The Fourth Hospital of Hebei Medical University Shijiazhuang 050011, China
| | - Qun Zhao
- The Third Department of Surgery, The Fourth Hospital of Hebei Medical University Shijiazhuang 050011, China
| | - Dong Wang
- The Third Department of Surgery, The Fourth Hospital of Hebei Medical University Shijiazhuang 050011, China
| | - Nan Jia
- The Third Department of Surgery, The Fourth Hospital of Hebei Medical University Shijiazhuang 050011, China
| | - Ying-Jie Hao
- The Third Department of Surgery, The Fourth Hospital of Hebei Medical University Shijiazhuang 050011, China
| |
Collapse
|
|
14
|
Roshankhah S, Mansouri K, Bakhtiari M, Salahshoor MR, Asgari R. Synergistic effects of TIMP2-418G/C and MMP9-1562C/T variants on the male infertility risk. Mol Biol Rep 2018; 46:861-866. [PMID: 30515695 DOI: 10.1007/s11033-018-4541-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2018] [Accepted: 11/28/2018] [Indexed: 11/26/2022]
Abstract
Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) involve in the degradation of the extracellular matrix (ECM) that imbalances their activity and may lead to various diseases. The present study aims to evaluate the association between MMP9-1562C/T and TIMP2-418G/C variants and synergistic effects of both variants on male infertility in an Iranian population. We analyzed these polymorphisms in 101 infertile men and 106 fertile men as a control group using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Based on the obtained results, no considerable association was observed in MMP9-1562C/T polymorphism frequency between infertile men and controls while frequencies of TIMP2-418G/C variant were significantly different in infertile and control groups (P = 0.028). Men with CC, GC and CC + GC genotypes for TIMP2-418G/C polymorphism had an increased risk of infertility compared to men with GG genotype [OR = 1.85, 95% CI (0.917-3.734, P = 0.086), OR = 1.94, 95% CI (1.098-3.437, P = 0.023) and OR = 2.053 95% CI (1.179-3.577, P = 0.011), respectively]. Also, in the presence of both TIMP2-418C and MMP9-1562T alleles the male infertility risk was significantly increased (P = 0.032). The current study suggests that the variation of TIMP2 gene and its interaction with MMP9 gene might be associated with male infertility. However, to confirm these findings, further studies are required in different ethnicities and with a larger sample size.
Collapse
Affiliation(s)
- Shiva Roshankhah
- Fertility and Sterility Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Kamran Mansouri
- Medical Biology Research Center (MBRC), Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mitra Bakhtiari
- Fertility and Sterility Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mohammad Reza Salahshoor
- Fertility and Sterility Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Rezvan Asgari
- Medical Biology Research Center (MBRC), Kermanshah University of Medical Sciences, Kermanshah, Iran.
| |
Collapse
|
|
15
|
Hu C, Weng F, Li L, Dai W, Yan J, Peng L, Zhou R. Association between MMP-9 -1562 C/T polymorphism and susceptibility to digestive cancers: A meta-analysis. Gene 2018; 673:88-94. [PMID: 29890308 DOI: 10.1016/j.gene.2018.06.025] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Revised: 04/21/2018] [Accepted: 06/08/2018] [Indexed: 11/18/2022]
Abstract
PURPOSE Matrix metalloproteinases (MMPs) play important roles in tumorigenesis. The variant in MMP-9 -1562 C/T (single nucleotide polymorphisms labeled rs3918242) has been extensively evaluated as predisposing factors to digestive cancers susceptibility. However, most of these studies only contained a small number of subjects and they showed conflicting results. Therefore, to elucidate these associations, we carried out a large-scale meta-analysis to provide this accurately comprehensive synopsis of case-control studies. METHODS A comprehensive literature search was conducted in EMBASE, OVID, Medline, China National Knowledge Internet and Wanfang for relevant data published between Jan 2000 and Mar 2018. Overall and stratified analyses based on the cancer types, ethnicity and source of control were carried out. Odds ratios (ORs) correspondent to 95% confidence intervals (95% CIs) were calculated to evaluate the genetic correlation between the variant and digestive cancer susceptibility. Review Manager 5.2 and Stata 12.0 were used for statistical analysis. RESULTS Twenty studies containing 3201 digestive cancer patients and 4301 matched-controls were screened out. The overall results suggested that MMP-9 -1562 C/T polymorphism increased the susceptibility to digestive cancers under homozygote and recessive models (homozygote, OR = 1.35, 95% CI 1.00-1.82, P = 0.05; recessive, OR = 1.42, 95% CI 1.07-1.88, P = 0.02). Furthermore, in the subgroup analysis based on the source of control, similar conclusions were obtained in the population-based control subgroup (homozygote, OR = 1.63, 95% CI 1.16-2.27, P = 0.004; recessive, OR = 1.67, 95% CI 1.22-2.28, P = 0.001), but not in the hospital-based control. In subgroup analyses based on cancer types and ethnicity, no association was observed. CONCLUSIONS Our meta-analysis suggested that MMP-9 -1562 C/T polymorphism might be related to the digestive cancer susceptibility. Evidence with adequate sample size is needed.
Collapse
Affiliation(s)
- Chaoliang Hu
- Department of Critical Care Medicine, Wuhan No.1 Hospital, Wuhan, China
| | - Fangzhong Weng
- Department of Critical Care Medicine, Wuhan No.1 Hospital, Wuhan, China
| | - Lin Li
- Department of Critical Care Medicine, Wuhan No.1 Hospital, Wuhan, China
| | - Wei Dai
- Department of Critical Care Medicine, Wuhan No.1 Hospital, Wuhan, China
| | - Jun Yan
- Department of Critical Care Medicine, Wuhan No.1 Hospital, Wuhan, China
| | - Liqing Peng
- Department of Critical Care Medicine, Wuhan No.1 Hospital, Wuhan, China
| | - Ruixiang Zhou
- Department of Critical Care Medicine, Wuhan No.1 Hospital, Wuhan, China.
| |
Collapse
|
|
16
|
Peng Z, Jia J, Gong W, Gao X, Ma P, Jin Z, Fan Y, Li Y, Zhang X. The association of matrix metalloproteinase-9 promoter polymorphisms with gastric cancer risk: a meta-analysis. Oncotarget 2017; 8:99024-99032. [PMID: 29228747 PMCID: PMC5716787 DOI: 10.18632/oncotarget.20931] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2017] [Accepted: 08/26/2017] [Indexed: 12/11/2022] Open
Abstract
Purpose A variety of studies have observed that the single nucleotide polymorphisms (SNPs) matrix metalloproteinase-9 (MMP-9) gene may be associated with the risk of gastric cancer(GC), and a cytosine (C) to thymine (T) mutation at the -1562 site of the MMP-9 gene promoter is reported to be closely related to the susceptibility. However, because of the conflicting results of these studies, we undertook a systematic meta-analysis to assess the association between the SNPs and the risk of gastric cancer. Materials and Methods A computerised literature search was conducted within the databases of PubMed, EMBASE, and ISI Web of Knowledge for studies on the genetic association of MMP-9-1562C/T and gastric cancer published from 2004 to 2015. The pooled odds ratio (OR) and 95% confidence intervals (CI) were estimated for each genotype using the dominant, recessive, co-dominant, and allelic models of the matrix metalloproteinase 9. Results Our analysis indicated a significant association of MMP-9-1562C/T with gastric cancer (dominant model [CT+TT/CC]: OR = 1.121, 95% CI = 0.965–1.304; recessive model [CC+CT/TT]: OR = 1.663, 95% CI = 1.148–2.408; co-dominant model [TT/CC]: OR = 1.666, 95% CI = 1.127–2.461; [CT/CC]: OR = 1.078, 95% CI = 0.923–1.259; allelic model [T/C]: OR = 1.150, 95% CI =1.014–1.304). Conclusions Our meta-analysis results demonstrated that MMP-9-1562C/T promoter polymorphisms increase the risk of developing gastric cancer.
Collapse
Affiliation(s)
- Ziheng Peng
- Department of School of Basic Medical Sciences, Hebei Medical University, Shi Jiazhuang 050017, China
| | - Jinhai Jia
- Department of Outpatient Clinic, Hebei Medical University, Shi Jiazhuang 050017, China
| | - Wenjian Gong
- Department of School of Basic Medical Sciences, Hebei Medical University, Shi Jiazhuang 050017, China
| | - Xuehan Gao
- Department of School of Basic Medical Sciences, Hebei Medical University, Shi Jiazhuang 050017, China
| | - Peiru Ma
- Department of School of Basic Medical Sciences, Hebei Medical University, Shi Jiazhuang 050017, China
| | - Zhucheng Jin
- Department of School of Basic Medical Sciences, Hebei Medical University, Shi Jiazhuang 050017, China
| | - Yue Fan
- Department of School of Basic Medical Sciences, Hebei Medical University, Shi Jiazhuang 050017, China
| | - Yanchu Li
- Department of School of Basic Medical Sciences, Hebei Medical University, Shi Jiazhuang 050017, China
| | - Xiaolin Zhang
- Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Shi Jiazhuang 050017, China
| |
Collapse
|
|
17
|
Associations of MMP-2 and MMP-9 gene polymorphism with ulinastatin efficacy in patients with severe acute pancreatitis. Biosci Rep 2017; 37:BSR20160612. [PMID: 28779012 PMCID: PMC5569160 DOI: 10.1042/bsr20160612] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2016] [Revised: 07/10/2017] [Accepted: 08/04/2017] [Indexed: 01/11/2023] Open
Abstract
We aim to explore the associations between matrix metalloproteinase (MMP) MMP-2/MMP-9 gene polymorphism with ulinastatin (UTI) efficacy in treating severe acute pancreatitis (SAP). A total of 276 SAP patients were assigned into the control (n=135) and observation (n=141) groups. PCR-restriction fragment length polymorphism (PCR-RFLP) was used for genotype and allele frequency distribution. Relevance of MMP-2/MMP-9 genotypes with UTI efficacy was analyzed. The observation group showed lowered duration in symptoms (abdominal distension, abdominal pain, tenderness, and rebound tenderness) than the control group. Laboratory analysis (serum calcium, white blood cells, serum amylase, urine amylase, APACHE-II, and Balthazar CTIS scores) were decreased, while serum albumin levels increased after 7th day of therapy. The total effective rate of UTI for patients with MMP-2 C-1306T C/C genotype was higher than those with C/T and T/T genotypes after the 7th day of therapy, which was lower in patients with MMP-9 C-1562T C/C and C/T genotypes than those with T/T genotype. The duration for symptoms in patients with MMP-9 C-1562T T/T genotype was shorter than those with C/C and C/T genotypes, which was less in patients with MMP-2 C-1306T C/C genotype than those with C/T and T/T genotypes. The improvement values of APACHE-II and Balthazar CTIS scores for patients with MMP-2 C-1306T C/C genotype were higher than those with C/T and T/T genotypes, which for patients with MMP-9 C-1562T C/C and C/T genotypes were lower than those with T/T genotype. These results demonstrated that MMP-2/MMP-9 gene polymorphism was associated with UTI efficacy for SAP.
Collapse
|
|
18
|
Chen J, Liu H, Gao P, Hui Y, Yang Z, Zhang X, Xu P, Tian F, Fan T. Preliminary evaluation for Bit1 as a potential biomarker for squamous cell carcinoma and adenocarcinoma of esophagus. Tumour Biol 2017; 39:1010428317708267. [PMID: 28488526 DOI: 10.1177/1010428317708267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Mounting evidence has demonstrated that Bit1 has been investigated as an etiological factor for certain cancers, including esophageal squamous cell carcinoma reported in our previous study, but data regarding possible roles of Bit1 in esophageal squamous cell carcinoma and esophageal adenocarcinoma remain to be elucidated. The purpose of this study was to examine whether Bit1 can be a novel diagnostic marker for the patients with esophageal squamous cell carcinoma and esophageal adenocarcinoma. The results revealed that Bit1 level in esophageal squamous cell carcinoma was significantly higher than that in esophageal adenocarcinoma tissues ( p < 0.05); notably, Bit1 level in esophageal adenocarcinoma tissues was lower than that in paired normal tissues but no difference was found ( p > 0.05). Bit1 expression patterns were completely in accordance with matrix metalloproteinase 2 and Bcl-2 in esophageal squamous cell carcinoma and esophageal adenocarcinoma. In addition, Bit1, Bcl-2, and matrix metalloproteinase 2 expression patterns in different differentiated esophageal squamous cell carcinoma were higher than those in corresponding normal esophageal tissues. Bit1 expression in poorly differentiated esophageal squamous cell carcinoma was significantly higher than that in normal esophageal tissues ( p < 0.05) but not in moderately and well-differentiated esophageal squamous cell carcinoma. Matrix metalloproteinase 2 expression patterns in poorly and moderately differentiated esophageal squamous cell carcinoma were significantly higher than those in corresponding normal esophageal tissues ( p < 0.01) but not in well-differentiated esophageal squamous cell carcinoma tissue ( p > 0.05). Bcl-2 expression patterns in various differentiated esophageal squamous cell carcinoma were higher than those in corresponding normal esophageal tissues with no statistical differences ( p > 0.05). Importantly, Bit1 expression was positively correlated with both matrix metalloproteinase 2 and Bcl-2 expression in esophageal squamous cell carcinoma and esophageal adenocarcinoma tissues ( p < 0.05). Collectively, these preliminary data support further investigation of Bit1 as an important diagnostic factor for esophageal squamous cell carcinoma and esophageal adenocarcinoma.
Collapse
Affiliation(s)
- Jing Chen
- 1 Department of Oncology, The Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.,2 Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China
| | - Hongtao Liu
- 3 Laboratory for Cell Biology, School of Life Science, Zhengzhou University, Zhengzhou, China
| | - Pan Gao
- 2 Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China
| | - Yiran Hui
- 2 Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China
| | - Zhenzhen Yang
- 2 Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China
| | - Xiaqing Zhang
- 3 Laboratory for Cell Biology, School of Life Science, Zhengzhou University, Zhengzhou, China
| | - Peirong Xu
- 4 School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Fang Tian
- 5 Department of Pathophysiology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China
| | - Tianli Fan
- 2 Department of Pharmacology, School of Basic Medicine, Zhengzhou University, Zhengzhou, China
| |
Collapse
|
|
19
|
Proteolysis in Helicobacter pylori-Induced Gastric Cancer. Toxins (Basel) 2017; 9:toxins9040134. [PMID: 28398251 PMCID: PMC5408208 DOI: 10.3390/toxins9040134] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Revised: 04/03/2017] [Accepted: 04/06/2017] [Indexed: 12/15/2022] Open
Abstract
Persistent infections with the human pathogen and class-I carcinogen Helicobacter pylori (H. pylori) are closely associated with the development of acute and chronic gastritis, ulceration, gastric adenocarcinoma and lymphoma of the mucosa-associated lymphoid tissue (MALT) system. Disruption and depolarization of the epithelium is a hallmark of H. pylori-associated disorders and requires extensive modulation of epithelial cell surface structures. Hence, the complex network of controlled proteolysis which facilitates tissue homeostasis in healthy individuals is deregulated and crucially contributes to the induction and progression of gastric cancer through processing of extracellular matrix (ECM) proteins, cell surface receptors, membrane-bound cytokines, and lateral adhesion molecules. Here, we summarize the recent reports on mechanisms how H. pylori utilizes a variety of extracellular proteases, involving the proteases Hp0169 and high temperature requirement A (HtrA) of bacterial origin, and host matrix-metalloproteinases (MMPs), a disintegrin and metalloproteinases (ADAMs) and tissue inhibitors of metalloproteinases (TIMPs). H. pylori-regulated proteases represent predictive biomarkers and attractive targets for therapeutic interventions in gastric cancer.
Collapse
|
|
20
|
Okada R, Naito M, Hattori Y, Seiki T, Wakai K, Nanri H, Watanabe M, Suzuki S, Kairupan TS, Takashima N, Mikami H, Ohnaka K, Watanabe Y, Katsuura-Kamano S, Kubo M, Hamajima N, Tanaka H. Matrix metalloproteinase 9 gene polymorphisms are associated with a multiple family history of gastric cancer. Gastric Cancer 2017; 20:246-253. [PMID: 27053167 DOI: 10.1007/s10120-016-0608-2] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2015] [Accepted: 03/30/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND A family history of gastric cancer (GC) is a well-known risk factor of GC. Genetic variations in genes of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been related to the risk of GC, but their association with familial background is not clear. We investigated whether individuals with a multiple family history of GC have more risk genotypes of MMP/TIMP genes. METHODS We genotyped ten common functional polymorphisms of MMP/TIMP genes in 4427 individuals aged 35-69 years without a history of GC who were enrolled in the Japan Multi-institutional Collaborative Cohort Study. Individuals who have two or more first-degree relatives (parents and siblings) with GC were categorized as having a multiple family history. Odds ratios (ORs) for multiple family history compared with no family history were calculated. RESULTS MMP9 279QQ (rs17576) was more frequently observed in individuals whose both parents had a history of GC (n = 23) and in individuals for whom one parent and their sibling(s) had a history of GC (n = 36) compared with those with no family history (n = 3816) [30.4 % vs 11.6 %, OR 4.34, 95 % confidence interval (CI) 1.45-13.03 and 16.7 % vs 11.6 %, OR 2.26, 95 % CI 0.81-6.27 after adjustment for age, sex, and current smoking]. The population attributable fraction was 38.1 %. The haplotype MMP9-1562C/279Q/668Q was more frequently observed in individuals whose both parents had a history of GC and in individuals for whom one parent and their sibling(s) had a history of GC compared with those with no family history (OR 3.35, 95 % CI 0.75-14.96 and OR 3.51, 95 % CI 1.35-9.15 respectively). CONCLUSIONS MMP9 polymorphisms were associated with a multiple family history of GC. Screening for these genotypes together with familial background may help us to identify individuals at an increased risk of GC.
Collapse
Affiliation(s)
- Rieko Okada
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 4668550, Japan.
| | - Mariko Naito
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 4668550, Japan
| | - Yuta Hattori
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 4668550, Japan
| | - Toshio Seiki
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 4668550, Japan
| | - Kenji Wakai
- Department of Preventive Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 4668550, Japan
| | - Hinako Nanri
- Department of Public Health, Showa University School of Medicine, Tokyo, Japan
| | - Miki Watanabe
- Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.,Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Sadao Suzuki
- Department of Public Health, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Tara Sefanya Kairupan
- Department of International Island and Community Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Naoyuki Takashima
- Department of Health Science, Shiga University of Medical Science, Otsu, Japan
| | - Haruo Mikami
- Division of Cancer Prevention and Epidemiology, Cancer Prevention Center, Chiba Cancer Center Research Institute, Chiba, Japan
| | - Keizo Ohnaka
- Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Yoshiyuki Watanabe
- Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine Graduate School of Medical Science, Kyoto, Japan
| | - Sakurako Katsuura-Kamano
- Department of Preventive Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan
| | - Michiaki Kubo
- RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
| | - Nobuyuki Hamajima
- Department of Healthcare Administration, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Hideo Tanaka
- Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan.,Department of Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | | |
Collapse
|
|
21
|
Does MMP-9 Gene Polymorphism Play a Role in Pituitary Adenoma Development? DISEASE MARKERS 2017; 2017:5839528. [PMID: 28194042 PMCID: PMC5282418 DOI: 10.1155/2017/5839528] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/01/2016] [Accepted: 11/23/2016] [Indexed: 12/19/2022]
Abstract
Purpose. To determine if the MMP-9 genotype has an influence on development of pituitary adenoma (PA). Methodology. The study enrolled n = 86 patients with PA and n = 526 healthy controls (reference group). The genotyping of MMP-9 was carried out using the real-time polymerase chain reaction method. Results. Our data demonstrated that the MMP-9 (–1562) C/C genotype was more frequent in PA group than in healthy controls (81.4% versus 64.6%, p = 0.002); C/C genotype was more frequently present in PA females compared to healthy control females, 81.5% versus 64.6%, p = 0.018, as well. MMP-9 (–1562) C/C genotype was frequently observed for all subgroups: noninvasive and invasive, nonrecurrence, and inactive PA compared to healthy controls: 81.8% versus 64.6%, p = 0.021; 81.0% versus 64.6%, p = 0.041; 81.8% versus 64.6%, p = 0.005; 100.0% versus 64.6%, p < 0.001, respectively. MMP-9 (–1562) C/C genotype was more frequent in inactive PA compared to active PA: 100.0% versus 71.4%; p < 0.001. Conclusion. MMP-9 (–1562) C/C genotype plays a role in nonrecurrence, inactive, and invasive as well as in nonivasive PA development.
Collapse
|
|
22
|
AbdRaboh NR, Bayoumi FA. Gene polymorphism of matrix metalloproteinases 3 and 9 in breast cancer. GENE REPORTS 2016. [DOI: 10.1016/j.genrep.2016.10.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
|
|
23
|
Yang Y, Xiong Y, Li J, Wu C, Jiang J. Association of TIMP-2-418G/C and TIMP-2-303G/A with gastric cancer: a meta-analysis. Onco Targets Ther 2016; 9:6801-6808. [PMID: 27843330 PMCID: PMC5098565 DOI: 10.2147/ott.s114113] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
Background According to the relevant reports, TIMP-2 polymorphism might be associated with the susceptibility to gastric cancer. Owing to the inconclusive results from the published studies based on the association between TIMP-2 single nucleotide polymorphisms (SNPs) and gastric cancer susceptibility, a meta-analysis was conducted to investigate the correlation between the TIMP-2 SNPs and the risk of gastric cancer. Materials and methods PubMed, Embase, CNKI and Wanfang databases were systematically searched to cover all the studies based on the association of two SNPs with the susceptibility to gastric cancer published before April 2016. Pooled odds ratios (ORs) and 95% confidence intervals were calculated for all genetic models. Results A total of six case–control studies on TIMP-2-418G/C and four studies on TIMP-2-303G/A were included. No obvious association was found between TIMP-2-418G/C polymorphism and the risk of gastric cancer in all the genetic models. On the other hand, TIMP-2-303G/A polymorphism had a significant association with increased risk of gastric cancer in homozygote recessive and allele comparisons, and similar results were observed in subgroups of Asian populations, but there were inadequate data to completely verify the association between TIMP-2-303G/A and gastric cancer. Conclusion TIMP-2-418G/C polymorphism is not correlated with the risk of gastric cancer, while TIMP-2-303G/A is a risk factor for gastric cancer, especially in Asian populations. However, owing to the limited cases, the results of TIMP-2-303G/A should be thoroughly examined and validated with large-scale and well-designed studies.
Collapse
Affiliation(s)
- Yan Yang
- Department of Tumor Biological Treatment, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu, People's Republic of China
| | - Yuqi Xiong
- Department of Tumor Biological Treatment, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu, People's Republic of China
| | - Jing Li
- Department of Tumor Biological Treatment, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu, People's Republic of China
| | - Changping Wu
- Department of Tumor Biological Treatment, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu, People's Republic of China
| | - Jingting Jiang
- Department of Tumor Biological Treatment, The Third Affiliated Hospital, Soochow University, Changzhou, Jiangsu, People's Republic of China
| |
Collapse
|
|
24
|
Banday MZ, Sameer AS, Mir AH, Mokhdomi TA, Chowdri NA, Haq E. Matrix metalloproteinase (MMP) -2, -7 and -9 promoter polymorphisms in colorectal cancer in ethnic Kashmiri population - A case-control study and a mini review. Gene 2016; 589:81-89. [PMID: 27222481 DOI: 10.1016/j.gene.2016.05.028] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2016] [Revised: 04/12/2016] [Accepted: 05/17/2016] [Indexed: 12/11/2022]
Abstract
Matrix metalloproteinases (MMPs) are proteolytic enzymes that play a pivotal role in the transformation and progression of tumors at all stages, especially during the invasion and metastasis. The aim of this study was to determine the genetic association of MMP2, MMP7 and MMP9 promoter polymorphisms with colorectal cancer (CRC) susceptibility and development risk in ethnic Kashmiri population. The genotype frequencies of MMP2-1306C/T, MMP7-181A/G and MMP9-1562C/T SNPs were compared between 142 CRC patients and 184 healthy controls by using PCR-RFLP method. The association between all the three MMP promoter polymorphisms and the modulation of risk of CRC was found to be significant (p≤0.05). The heterozygous genotype (CT) of MMP2-1306C/T SNP and variant genotype (GG) of MMP7-181A/G SNP showed a significant association with decreased risk for the development of CRC [OR, 0.61 (95%CI, 0.37-1.01); p=0.05 and OR, 0.43 (95%CI, 0.20-0.90); p=0.02, respectively] whereas the heterozygous genotype (CT) of MMP9-1562C/T SNP showed a significant association with increased risk for the development of colorectal cancer [OR, 1.88 (95%CI, 1.11-3.18); p=0.02]. Further, the less common MMP9-1562T allele was found to be significantly associated with an increased risk of colorectal cancer [OR, 1.74 (95%CI, 1.15-2.62); p=0.007]. Our results suggest that these MMP2, MMP7 and MMP9 promoter polymorphisms play a role as one of the key modulators of the risk of developing colorectal cancer in Kashmiri population.
Collapse
Affiliation(s)
- Mujeeb Zafar Banday
- Department of Biotechnology, University of Kashmir, Hazratbal, Srinagar, Kashmir, India
| | - Aga Syed Sameer
- Department of Basic Medical Sciences, College of Medicine, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia
| | - Ashaq Hussain Mir
- Department of Biotechnology, University of Kashmir, Hazratbal, Srinagar, Kashmir, India
| | - Taseem A Mokhdomi
- Department of Biotechnology, University of Kashmir, Hazratbal, Srinagar, Kashmir, India
| | - Nissar A Chowdri
- Department of Surgery, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India
| | - Ehtishamul Haq
- Department of Biotechnology, University of Kashmir, Hazratbal, Srinagar, Kashmir, India.
| |
Collapse
|
|
25
|
Verma S, Kesh K, Gupta A, Swarnakar S. An Overview of Matrix Metalloproteinase 9 Polymorphism and Gastric Cancer Risk. Asian Pac J Cancer Prev 2015; 16:7393-400. [DOI: 10.7314/apjcp.2015.16.17.7393] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
|
|
26
|
Yari K, Rahimi Z, Payandeh M, Rahimi Z. MMP-7 A-181G Polymorphism in Breast Cancer Patients from Western Iran. Breast Care (Basel) 2015; 10:398-402. [PMID: 26989359 PMCID: PMC4789881 DOI: 10.1159/000442231] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND Matrix metalloproteinases (MMPs) are upregulated in tumors. The MMP-7 A-181G polymorphism is associated with increased expression of the MMP-7 gene. Aim of the present study was to investigate the association between the MMP-7 A-181G polymorphism and susceptibility to breast cancer. PATIENTS AND METHODS The MMP-7 A-181G variants were studied in a cohort of 251 subjects consisting of 100 breast cancer patients and 151 healthy controls; all were from Western Iran. The MMP-7 A-181G genotypes were identified using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS The frequencies of the MMP-7 AA, AG, and GG genotypes in healthy individuals were 34.4, 50.4, and 15.2%, respectively. In breast cancer patients, the frequencies of AA (34%), AG (52%), and GG (14%) genotypes (p = 0.95) were similar to those in the controls. There was a trend toward an increased frequency of the combined genotype of MMP-7 AG+GG in patients with lymph node metastasis (70.4%) compared to those without metastasis (66.7%). Also, in patients with invasive lobular carcinoma, the frequency of the MMP-7 AG+GG genotype tended to be higher (71.4%) compared to that in patients with invasive ductal carcinoma (66.2%) (p = 0.78). CONCLUSION Our findings indicate that the MMP-7 A-181G polymorphism may not be correlated with susceptibility to breast cancer in our population.
Collapse
Affiliation(s)
- Kheirollah Yari
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Ziba Rahimi
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mehrdad Payandeh
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Zohreh Rahimi
- Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
- Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran
| |
Collapse
|
|
27
|
Singh N, Hussain S, Sharma U, Suri V, Nijhawan R, Bharadwaj M, Sobti RC. The protective role of the -1306C>T functional polymorphism in matrix metalloproteinase-2 gene is associated with cervical cancer: implication of human papillomavirus infection. Tumour Biol 2015; 37:5295-303. [PMID: 26561467 DOI: 10.1007/s13277-015-4378-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2015] [Accepted: 11/04/2015] [Indexed: 10/22/2022] Open
Abstract
Cervical cancer is the major reproductive health problem among women caused by persistent infection of high-risk human papillomavirus (HR-HPV). Metalloproteinase-2 (MMP-2) is an endopeptidase highly expressed in cervical cancer; however, the genetic link between aberrant expression of MMP-2 and cervical carcinogenesis is not known. The genotypic distribution, expression pattern of MMP-2 and HPV infection, was analyzed in a total of 300 fresh surgically resected cervical tissue biopsies. The MMP-2 C1306T (rs243865) promoter polymorphism dominant model (CC v/s CT + CT + TT) revealed that the CC genotype had a 4.33-fold significant increased risk for development of cervical cancer (OR = 4.33; 95 % CI = 2.36-4.02, p = 0.0001) compared to those with variant genotypes (-1306 CT + TT). The C allele was associated with 3-fold significant increased risk (OR = 2.95; 95 % CI = 1.90-4.60, p = 0.0002) compared to T allele. Interestingly, a significant correlation was found between high expression of MMP-2 protein and CC genotype in cancer patients (p = 0.001) compared to normal controls (p = 0.012). Further analysis showed that the risk of cancer was extremely pronounced in HPV positive patients (OR = 9.33; 95 % CI = 2.88-30.20, p = 0.0001) compared to HPV negative ones, implicating the possible interaction between -1306CC genotype and HPV infection in increasing the cancer risk (p = 0.0001). The leads from the present study suggest the protective role of gene variant -1306C>T at the promoter region of the MMP-2 against HPV-mediated cervical cancer. These findings substantiate the functional role of MMP-2 C1306T polymorphism in a significant downregulation of MMP-2 protein in women with variant genotype (CT/TT) compared to the normal wild CC genotype.
Collapse
Affiliation(s)
- Neha Singh
- Systems Biology Research Centre-Tumor biology, School of Life Sciences, University of Skövde, Skövde, SE-54128, Sweden. .,Department of Biotechnology, Panjab University, Chandigarh, India.
| | - Showket Hussain
- Division of Molecular Oncology, Institute of Cytology and Preventive Oncology (ICMR), Noida, India.
| | - Upma Sharma
- Division of Molecular Genetics and Biochemistry, Institute of Cytology and Preventive Oncology (ICMR), Noida, India
| | - Vanita Suri
- Department of Obstetrics and Gynecology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Raje Nijhawan
- Department of Cytology & Gynae. Pathology, Post Graduate Institute of Medical Education and Research, Sector-12, Chandigarh, India
| | - Mausumi Bharadwaj
- Division of Molecular Genetics and Biochemistry, Institute of Cytology and Preventive Oncology (ICMR), Noida, India
| | - R C Sobti
- Department of Biotechnology, Panjab University, Chandigarh, India. .,Vice Chancellor BBA (Central) University, Lucknow, India.
| |
Collapse
|
|
28
|
Wu Z, Jiang P, Zulqarnain H, Gao H, Zhang W. Relationship between single-nucleotide polymorphism of matrix metalloproteinase-2 gene and colorectal cancer and gastric cancer susceptibility: a meta-analysis. Onco Targets Ther 2015; 8:861-9. [PMID: 25945057 PMCID: PMC4406259 DOI: 10.2147/ott.s78031] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Background Recently, the published data on the association between matrix metalloproteinase-2 (MMP-2) (C-1306T) polymorphism and colorectal cancer (CRC) and gastric cancer (GC) (gastrointestinal cancer) risk remained controversial. The aim of this study is to investigate the relationship between the risk of CRC and GC and single-nucleotide polymorphism of MMP-2(C-1306T). Methods Medline, Embase, Science Citation Index, and PubMed were thoroughly searched to identify relevant studies. Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the association. Results We performed a meta-analysis of 14 studies including 642 cases and 692 controls for CRC and 1,936 cases and 3,490 controls for GC. The result indicates that there is significant relationship between MMP-2(C-1306T) polymorphism and CRC risk in recessive model and codominant model (TT vs CC/CT: OR: 2.39, 95% CI: 1.30–4.37, P=0.005; TT vs CC: OR: 2.36, 95% CI: 1.29–4.34, P=0.006). In subgroup analysis according to ethnicity, significant associations were found in Caucasians (TT vs CC/CT: OR: 2.87, 95% CI: 1.43–5.78, P=0.003; TT vs CC: OR: 2.86, 95% CI: 1.41–5.80, P=0.003), but we did not find significant evidence with GC in all genetic models, and in stratified analysis according to ethnicity, no significant risk was found in the subgroup too. Conclusion This meta-analysis considered that the MMP-2(C-1306T) polymorphism is a risk factor for CRC susceptibility, especially in Caucasians, but it does not support any relationship to GC, and further studies are needed to explore the association.
Collapse
Affiliation(s)
- Zesheng Wu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People's Republic of China
| | - Peng Jiang
- Department of Oncology, Tumor Hospital of Xinjiang Medical University, Urumqi, People's Republic of China
| | - Haider Zulqarnain
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People's Republic of China
| | - Hua Gao
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People's Republic of China
| | - Wenbin Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People's Republic of China
| |
Collapse
|
|
29
|
Kesh K, Subramanian L, Ghosh N, Gupta V, Gupta A, Bhattacharya S, Mahapatra NR, Swarnakar S. Association of MMP7 -181A→G Promoter Polymorphism with Gastric Cancer Risk: INFLUENCE OF NICOTINE IN DIFFERENTIAL ALLELE-SPECIFIC TRANSCRIPTION VIA INCREASED PHOSPHORYLATION OF cAMP-RESPONSE ELEMENT-BINDING PROTEIN (CREB). J Biol Chem 2015; 290:14391-406. [PMID: 25847246 DOI: 10.1074/jbc.m114.630129] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2014] [Indexed: 01/27/2023] Open
Abstract
Elevated expression of matrix metalloproteinase7 (MMP7) has been demonstrated to play a pivotal role in cancer invasion. The -181A→G (rs11568818) polymorphism in the MMP7 promoter modulates gene expression and possibly affects cancer progression. Here, we evaluated the impact of -181A→G polymorphism on MMP7 promoter activity and its association with gastric cancer risk in eastern Indian case-control cohorts (n = 520). The GG genotype as compared with the AA genotype was predisposed (p = 0.02; odds ratio = 1.9, 95% confidence interval = 1.1-3.3) to gastric cancer risk. Stratification analysis showed that tobacco addiction enhanced gastric cancer risk in GG subjects when compared with AA subjects (p = 0.03, odds ratio = 2.46, and 95% confidence interval = 1.07-5.68). Meta-analysis revealed that tobacco enhanced the risk for cancer more markedly in AG and GG carriers. Activity and expression of MMP7 were significantly higher in GG than in AA carriers. In support, MMP7 promoter-reporter assays showed greater transcriptional activity toward A to G transition under basal/nicotine-induced/cAMP-response element-binding protein (CREB) overexpressed conditions in gastric adenocarcinoma cells. Moreover, nicotine (a major component of tobacco) treatment significantly up-regulated MMP7 expression due to enhanced CREB phosphorylation followed by its nuclear translocation in gastric adenocarcinoma cells. Furthermore, chromatin immunoprecipitation experiments revealed higher binding of phosphorylated CREB with the -181G than the -181A allele. Altogether, specific binding of phosphorylated CREB to the G allele-carrying promoter enhances MMP7 gene expression that is further augmented by nicotine due to increased CREB phosphorylation and thereby increases the risk for gastric cancer.
Collapse
Affiliation(s)
- Kousik Kesh
- From the Drug Development Diagnostic and Biotechnology Division, Indian Institute of Chemical Biology, Kolkata 700032
| | - Lakshmi Subramanian
- the Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, and
| | - Nillu Ghosh
- From the Drug Development Diagnostic and Biotechnology Division, Indian Institute of Chemical Biology, Kolkata 700032
| | - Vinayak Gupta
- the Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, and
| | - Arnab Gupta
- the Saroj Gupta Cancer Center and Research Institute, Kolkata 700104, India
| | - Samir Bhattacharya
- the Saroj Gupta Cancer Center and Research Institute, Kolkata 700104, India
| | - Nitish R Mahapatra
- the Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai 600036, and
| | - Snehasikta Swarnakar
- From the Drug Development Diagnostic and Biotechnology Division, Indian Institute of Chemical Biology, Kolkata 700032,
| |
Collapse
|
|
30
|
Yang TF, Guo L, Wang Q. Meta-analysis of associations between four polymorphisms in the matrix metalloproteinases gene and gastric cancer risk. Asian Pac J Cancer Prev 2014; 15:1263-7. [PMID: 24606450 DOI: 10.7314/apjcp.2014.15.3.1263] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Matrix metalloproteinases (MMPs) play important roles in pathogenesis and development of cancer. Recently, many studies have show associations between polymorphisms in the promoter regions of MMPs and risk of gastric cancer. The present meta-analysis was conducted in order to investigate the potential association between four polymorphisms in the MMP gene and gastric cancer risk. METHODS A computerized literature search was conducted in databases of Med-line, Embase, Science Citation Index and PubMed till June 2013 for any MMP genetic association study of gastric cancer. Odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated for each gene under dominant and recessive models, and heterogeneity between studies was assessed using the Q test and I2 value. Overall and subgroup analyses according to ethnicity were carried out with Stata 12.0. RESULTS 14 reports covering 8,146 patients (2,980 in the case group and 5,166 in the control group) were included in the present meta-analysis. We found that the MMP-7 (-181A>G) polymorphism increased the gastric cancer risk in therecessive model (GG vs. AA/AG, OR=1.768, 95% CI =1.153-2.712). For MMP2 ?1306 C>T, MMP1-1607 1G/2G, and MMP9?1 562 C>T, there were no associations between these polymorphisms and the risk of gastric cancer under dominant or recessive models. CONCLUSION This meta-analysis suggested that the MMP7-181 A>G polymorphism may contribute to gastric cancer susceptibility. More studies are needed, especially in Europeans, in the future.
Collapse
Affiliation(s)
- Teng-Fei Yang
- Department of Gastroenterology Surgery, Affiliated Shengjing Hospital of China Medical University, Shenyang, China E-mail :
| | | | | |
Collapse
|
|
31
|
Song G, Yan J, Zhang Q, Li G, Chen ZJ. Association of tissue inhibitor of metalloproteinase gene polymorphisms and unexplained recurrent spontaneous abortions in Han Chinese couples. Eur J Obstet Gynecol Reprod Biol 2014; 181:84-8. [PMID: 25128867 DOI: 10.1016/j.ejogrb.2014.07.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2014] [Revised: 07/08/2014] [Accepted: 07/20/2014] [Indexed: 11/24/2022]
Abstract
OBJECTIVE To investigate the association of tissue inhibitor of metalloproteinase (TIMP) gene polymorphisms with unexplained recurrent spontaneous abortions (URSA) in a well-defined group of Han Chinese couples. STUDY DESIGN This is a case-control association study. Genomic DNA was extracted from peripheral blood samples from 84 couples with histories of three or more pregnancy losses and 69 age-matched healthy couples with at least one live birth and no histories of pregnancy loss. Polymerase chain reactions (PCRs) and sequencing with the fluorescent dye dideoxy-termination method were used to detect the rs4898 in TIMP-1, rs2277698 in TIMP-2, rs2234921 and rs5749511 in TIMP-3 and rs17035945 in TIMP-4 genotypes and allele frequencies. RESULTS Neither the allele frequencies nor any of the genetic model of the five TIMP gene SNPs (i.e., TIMP-1-rs4898, TIMP-2-rs2277698, TIMP-3-rs5749511 and rs2234921, and TIMP-4-rs7035945) were significantly differences between the URSA couples and the control group. CONCLUSIONS No evidence was found for any associations between the TIMP-1,-2,-3, or -4 genes SNPs with URSA in this Han Chinese Han.
Collapse
Affiliation(s)
- Guihong Song
- Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University, Jinan, China; Shandong College of Traditional Chinese Medicine, Yantai, China
| | - Junhao Yan
- Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China; The Key Laboratory for Reproductive Endocrinology of Ministry of Education, Jinan, China
| | - Qian Zhang
- Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University, Jinan, China
| | - Guangyu Li
- Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China; The Key Laboratory for Reproductive Endocrinology of Ministry of Education, Jinan, China
| | - Zi-Jiang Chen
- Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University, Jinan, China; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China; The Key Laboratory for Reproductive Endocrinology of Ministry of Education, Jinan, China.
| |
Collapse
|
|
32
|
Verma S, Kesh K, Ganguly N, Jana S, Swarnakar S. Matrix metalloproteinases and gastrointestinal cancers: Impacts of dietary antioxidants. World J Biol Chem 2014; 5:355-376. [PMID: 25225603 PMCID: PMC4160529 DOI: 10.4331/wjbc.v5.i3.355] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2014] [Revised: 05/07/2014] [Accepted: 06/11/2014] [Indexed: 02/05/2023] Open
Abstract
The process of carcinogenesis is tightly regulated by antioxidant enzymes and matrix degrading enzymes, namely, matrix metalloproteinases (MMPs). Degradation of extracellular matrix (ECM) proteins like collagen, proteoglycan, laminin, elastin and fibronectin is considered to be the prerequisite for tumor invasion and metastasis. MMPs can degrade essentially all of the ECM components and, most MMPs also substantially contribute to angiogenesis, differentiation, proliferation and apoptosis. Hence, MMPs are important regulators of tumor growth both at the primary site and in distant metastases; thus the enzymes are considered as important targets for cancer therapy. The implications of MMPs in cancers are no longer mysterious; however, the mechanism of action is yet to be explained. Herein, our major interest is to clarify how MMPs are tied up with gastrointestinal cancers. Gastrointestinal cancer is a variety of cancer types, including the cancers of gastrointestinal tract and organs, i.e., esophagus, stomach, biliary system, pancreas, small intestine, large intestine, rectum and anus. The activity of MMPs is regulated by its endogenous inhibitor tissue inhibitor of metalloproteinase (TIMP) which bind MMPs with a 1:1 stoichiometry. In addition, RECK (reversion including cysteine-rich protein with kazal motifs) is a membrane bound glycoprotein that inhibits MMP-2, -9 and -14. Moreover, α2-macroglobulin mediates the uptake of several MMPs thereby inhibit their activity. Cancerous conditions increase intrinsic reactive oxygen species (ROS) through mitochondrial dysfunction leading to altered protease/anti-protease balance. ROS, an index of oxidative stress is also involved in tumorigenesis by activation of different MAP kinase pathways including MMP induction. Oxidative stress is involved in cancer by changing the activity and expression of regulatory proteins especially MMPs. Epidemiological studies have shown that high intake of fruits that rich in antioxidants is associated with a lower cancer incidence. Evidence indicates that some antioxidants inhibit the growth of malignant cells by inducing apoptosis and inhibiting the activity of MMPs. This review is discussed in six subchapters, as follows.
Collapse
|
|
33
|
Mandal RK, Akhter N, Haque S, Panda AK, Mittal RD, Alqumber MAA. No correlation between TIMP2 -418 G>C polymorphism and increased risk of cancer: evidence from a meta-analysis. PLoS One 2014; 9:e88184. [PMID: 25136829 PMCID: PMC4138026 DOI: 10.1371/journal.pone.0088184] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2013] [Accepted: 06/30/2014] [Indexed: 11/24/2022] Open
Abstract
Aim Tissue inhibitor of metalloproteinase (TIMP2) is involved in the regulation of matrix metalloproteinase 2 (MMP2) and shown to implicate in cancer development and progression. The results from the published studies based on the association between TIMP2 -418 G>C polymorphism and cancer risk are inconsistent. In this meta-analysis, we aimed to evaluate the potential association between TIMP2 -418 G>C polymorphism and cancer risk. Methodology We searched PubMed (Medline) and EMBASE web databases to cover all studies based on relationship of TIMP2 -418 G>C polymorphism and risk of cancer until October 2013. The meta-analysis was performed for selected case-control studies and pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for all genetic models. Results A total of 2225 cancer cases and 2532 controls were included from ten eligible case-control studies. Results from overall pooled analysis suggested no evidence of significant risk between TIMP2 -418 G>C polymorphism and cancer risk in any of the genetic models, such as, allele (C vs. G: OR = 1.293, 95% CI = 0.882 to 1.894, p = 0.188), homozygous (CC vs. GG: OR = 0.940, 95% CI = 0.434 to 2.039, p = 0.876), heterozygous (GC vs. GG: OR = 1.397, 95% CI = 0.888 to 2.198, p = 0.148), dominant (CC+GC vs. GG: OR = 1.387, 95% CI = 0.880 to 2.187, p = 0.159) and recessive (CC vs. GG+GC: OR = 0.901, 95% CI = 0.442 to 1.838, p = 0.774) models. No evidence of publication bias was detected during the analysis. Conclusions The present meta-analysis suggests that the TIMP2 -418 G>C polymorphism may not be involved in predisposing risk factor for cancer in overall population. However, future larger studies with group of populations are needed to analyze the possible correlation.
Collapse
Affiliation(s)
- Raju K. Mandal
- Department of Urology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Naseem Akhter
- Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Albaha University, Albaha, Saudi Arabia
| | - Shafiul Haque
- Department of Biosciences, Jamia Millia Islamia (A Central University), New Delhi, India
| | - Aditya K. Panda
- Department of Infectious Disease Biology, Institute of Life Sciences, Bhubaneswar, Odisha, India
| | - Rama D. Mittal
- Department of Urology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
| | - Mohammed A. A. Alqumber
- Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Albaha University, Albaha, Saudi Arabia
- * E-mail:
| |
Collapse
|
|
34
|
Gurgel DC, Valença-Junior JT, Dornelas CA, Vieira RB, Maia-Filho JTA, Lima-Junior RCP, Ribeiro RA, Almeida PRC. Immunoexpression of metalloproteinases 2 and 14 and TIMP-2 inhibitor in main types of primary gastric carcinomas and lymph node metastasis. Pathol Oncol Res 2014; 21:73-81. [PMID: 24800696 DOI: 10.1007/s12253-014-9790-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2013] [Accepted: 04/21/2014] [Indexed: 12/18/2022]
Abstract
Metalloproteinase-2 (MMP-2) and -14 (MMP-14) and the tissue inhibitor of metalloproteinases type 2 (TIMP-2) participate in epithelial-mesenchymal transition and tumor progression in many cancers. However, the correlation between these enzymes in gastric cancer and the metastatic potential to their respective lymph node needs to be determined. Here, we evaluated the expression of these enzymes in gastric carcinoma and lymph node metastases and their possible involvement in tumor progression. Histological samples from 83 patients with gastric cancer and their respective lymph nodes were used. MMP-2, MMP-14 and TIMP-2 immunoexpression was scored. TIMP-2 expression in tumor-associated macrophages occurred more frequently than in normal mucosa (P = 0.0128). Female tumor samples presented higher MMP-2 expression (P = 0.0248), while TIMP-2 occurred mainly in patients over 50 years old (P = 0.0034). MMP-2 was higher expressed in primary tumor macrophages than in neoplastic cells (P = 0.0118), and was also seen in macrophages from metastatic-affected lymph nodes of intestinal and diffuse histotypes (P = 0.0006). MMP-2, MMP-14 and TIMP-2 expression in mononuclear cells might be correlated with progression of gastric cancer. MMP-14 production by macrophages appears to be more involved in diffuse gastric cancer progression.
Collapse
Affiliation(s)
- Daniel Cordeiro Gurgel
- Department of Pathology and Forensic Medicine, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil,
| | | | | | | | | | | | | | | |
Collapse
|
|
35
|
Serum levels and tissue expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinases 2 (TIMP-2) in colorectal cancer patients. Tumour Biol 2014; 35:3793-802. [PMID: 24395652 PMCID: PMC3980035 DOI: 10.1007/s13277-013-1502-8] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2013] [Accepted: 11/29/2013] [Indexed: 11/04/2022] Open
Abstract
The objective of the study was the assessment of serum levels and tissue expression of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of matrix metalloproteinases 2 (TIMP-2) in patients with colorectal cancer (CRC). The study included 72 CRC patients and 68 healthy subjects. The serum levels of MMP-2 and TIMP-2 were measured using enzyme-linked immunosorbent assay (ELISA) method, whereas tissue expression of MMP-2 and TIMP-2 in cancer cells, interstitial inflammatory cells, and adjacent normal colorectal mucosa were examined by immunohistochemical staining of tumor samples. The serum levels of MMP-2 and TIMP-2 in cancer patients were significantly lower than those in control group, but the percentage of positive immunoreactivity of these proteins were higher in malignant and inflammatory cells as compared to normal tissue. There was a significant correlation between MMP-2 immunoreactivity in inflammatory cells and the presence of distant metastases and between TIMP-2 expression in inflammatory cells and tumor size, nodal involvement, and distant metastases. Area under receiver operating characteristic (ROC) curve (AUC) for serum MMP-2 was higher than for serum TIMP-2. Moreover, positive tissue expression of MMP-2 was a significant prognostic factor for CRC patients’ survival. Our findings suggest that MMP-2 and TIMP-2 might play a role in the process of colorectal cancer invasion and metastasis, but the significance of their interactions with tumor stroma and interstitial inflammatory infiltration in colorectal neoplasia require further elucidation.
Collapse
|
|
36
|
Matrix metalloproteinase7 -181A/G polymorphism is associated with increased cancer risk among high-quality studies: Evidence from a meta-analysis. Clin Biochem 2013; 46:1649-54. [DOI: 10.1016/j.clinbiochem.2013.07.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2012] [Revised: 06/15/2013] [Accepted: 07/15/2013] [Indexed: 01/15/2023]
|
|
37
|
Markiewicz L, Majsterek I, Przybylowska K, Dziki L, Waszczyk M, Gacek M, Kaminska A, Szaflik J, Szaflik JP. Gene polymorphisms of the MMP1, MMP9, MMP12, IL-1β and TIMP1 and the risk of primary open-angle glaucoma. Acta Ophthalmol 2013; 91:e516-23. [PMID: 23800300 DOI: 10.1111/aos.12149] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
BACKGROUND Primary open-angle glaucoma (POAG) is the main cause of irreversible blindness worldwide. Matrix metalloproteinases (MMPs) and their regulators (TIMPs and ILs) have been extensively studied as POAG risk factors. Recent reports have showed several single-nucleotide polymorphisms (SNPs) for MMPs, TIMPs and ILs encoding genes in patients with POAG. The aim of this study was to investigate association of the -1607 1G/2G MMP1, -the 1562 C/T MMP9, the -82 A/G MMP12, the -511 C/T IL-1β and the 372 T/C TIMP1 gene polymorphisms with POAG occurrence and to investigate their impact on main clinical features. MATERIAL AND METHODS In the present case-control study, we examined group of 511 unrelated Caucasian subjects consist of 255 patients with POAG (mean age 70 ± 15) and 256 controls (mean age 67 ± 16). Determination of genes polymorphic variants was made using polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP). The odds ratios (ORs) and 95% confidence intervals (CIs) for each genotype and allele were calculated. RESULTS Presented study showed statistically significant increase in the POAG development risk of the -1607 2G/2G MMP1 genotype (OR 1.75; 95% CI, 1.11-2.75; p = 0.014) and for the -1607 2G MMP1 allele (OR 1.35; 95% CI, 1.05-1.73; p = 0.017), as well as for the -1562 C/T MMP9 genotype (OR 1.74; 95% CI, 1.17-2.59; p = 0.006) and the -1562 T MMP9 allele (OR 1.55; 95% CI, 1.10-2.17; p = 0.012) in patients with POAG in comparison with healthy control group. We also observed positive association of the -511 T/T IL-1β genotype (OR 2.60; 95% CI, 1.41-4.80; p = 0.002) as well as the -511 T IL-1β allele occurrence with an increased POAG development risk (OR 1.47; 95% CI, 1.13-1.90; p = 0.003). Furthermore, we found an association of the -1607 1G/2G MMP1, -1562 C/T MMP9 (anova, p < 0.001) and the -511 C/T IL-1β gene polymorphism (anova, p < 0.05) with decreased retinal nerve fibre layer (RNFL) thickness in patients with POAG group. Results displayed also an association of the 372 T/C TIMP1 gene polymorphism with normal range RNFL (anova, p < 0.001). We observed an association of decreased RA value (rim area) with the -82 A/G MMP12 (anova, p < 0.001). Normal RA value was observed in patients with POAG group connected with the 372 T/C TIMP1 (anova, p < 0.05) and the -511 C/T IL-1β (anova, p < 0.05) genes polymorphisms occurrence. Finally, results showed an association of the -1562 C/T MMP9 (anova, p < 0.001) gene polymorphism with decreased cup/disc index in patients with POAG group. CONCLUSION In conclusion, we suggest that the -1607 1G/2G MMP1, -1562 C/T MMP9, -511 C/T IL-1β gene polymorphisms can be considered as an important risk factors associated with POAG.
Collapse
Affiliation(s)
- Lukasz Markiewicz
- Department of Clinical Chemistry and Biochemistry, Medical University of Lodz, Lodz, PolandDepartment of General and Colorectal Surgery, Medical University of Lodz, Lodz, PolandDepartment of Ophthalmology, Medical University of Warsaw, Warsaw, Poland
| | | | | | | | | | | | | | | | | |
Collapse
|
|
38
|
Li X, Qu L, Zhong Y, Zhao Y, Chen H, Daru L. Association between promoters polymorphisms of matrix metalloproteinases and risk of digestive cancers: a meta-analysis. J Cancer Res Clin Oncol 2013; 139:1433-47. [PMID: 23644699 DOI: 10.1007/s00432-013-1446-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2013] [Accepted: 02/21/2013] [Indexed: 12/11/2022]
Abstract
PURPOSE A variety of studies have been performed to elucidate the polymorphisms in promoter regions of matrix metalloproteinases (MMPs) associated with the risk of digestive cancers, and yet, results remain conflicting and heterogeneous. Thus, we undertook a systematic meta-analysis to determine the genetic susceptibility of MMPs to digestive cancers. METHODS A computerized literature search was conducted in databases of PubMed, Embase, and ISI Web of Knowledge till October 2012 for any MMP genetic association study in oral squamous, gastric, esophageal, and colorectal carcinomas. Odds ratios (OR) and 95 % confidence interval (CI) were estimated for each gene under dominant and recessive models, and the heterogeneity between studies was assessed using Q test and I (2) value. Overall and subgroup analysis according to anatomical sites and ethnicity was carried out. Statistical analysis was performed with Review Manager 5.0. RESULTS A total of 40 eligible publications with 68 comparisons were included in this study. For MMP1 nt-1607, individuals with 2G state could increase risk of digestive cancers in total analysis (dominant: OR = 1.31, 95 % CI = 1.16-1.48, P < 0.00001; recessive: OR = 1.29, 95 % CI = 1.11-1.50, P = 0.0009). In the subgroup of tumor sites, significant associations were also observed in esophageal cancer and colorectal cancer under both genetic models. For MMP2 nt-1306, CT or TT carriers performed significant protection against digestive cancer in the dominant model (OR = 0.69, 95 % CI = 0.55-0.85, P = 0.0007) of the overall. In the subgroup analysis, significant association was found in esophageal cancer, with borderline effects in gastric cancer and oral squamous cell carcinoma. For MMP7 -181 A/G, significant association was observed under two genetic models in the overall (dominant: OR = 1.26, 95 % CI = 1.10-1.43, P = 0.0009; recessive: OR = 1.33, 95 % CI = 1.11-1.60, P = 0.002) and in the individual cancer subgroup of esophageal cancer and gastric cancer. For MMP9 -1,562 C/T, a borderline effect was found with digestive cancers in the total and stratified analysis of the colorectal cancer under dominant model. No association was observed in either the overall or subgroup analysis for MMP3 -1,171 5A/6A. CONCLUSIONS Our meta-analysis demonstrated the fact that polymorphisms in promoter regions of MMP genes might be related to the susceptibility of digestive cancers, with cancer development for MMP1 and MMP7, and a protection against cancer for MMP2 and MMP9. Further evidences with adequate sample sizes need to be conducted.
Collapse
Affiliation(s)
- Xiaoying Li
- State Key Laboratory of Genetic Engineering, Fudan-VARI Genetic Epidemiology Center and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, 200433, People's Republic of China
| | | | | | | | | | | |
Collapse
|
|
39
|
Wang MF, Kuo SH, Huang CH, Chen YJ, Lin SH, Lee CJ, Lue KH, Wu SC, Cho CY, Wong RH. Exposure to environmental tobacco smoke, human E-cadherin C-160A polymorphism, and childhood asthma. Ann Allergy Asthma Immunol 2013; 111:262-7. [PMID: 24054361 DOI: 10.1016/j.anai.2013.07.008] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2013] [Revised: 06/19/2013] [Accepted: 07/10/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND Environmental tobacco smoke (ETS) is a risk factor for asthma. Importantly, cigarette smoke can decrease the adherence of epithelial cells and increase detachment. The adhesion molecule E-cadherin (CDH1) has an essential role in the formation of epithelial junction. Turnover of the extracellular matrix, which is characterized by airway remodeling, depends on the imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs). OBJECTIVE To evaluate the effects of ETS exposure and CDH1, MMP-3, and TIMP-1 genetic polymorphisms on childhood asthma. METHODS The CDH1 C-160A, MMP-3 -1171, and TIMP-1 T372C genotypes were identified by polymerase chain reaction in 299 asthmatic children and 383 healthy controls. RESULTS More ETS exposure (>5 vs 0 cigarettes/day; odds ratio [OR], 1.45; 95% confidence interval [CI], 1.05-2.01) and the presence of CDH1 AA/CA genotypes (OR, 1.53; 95% CI, 1.08-2.17) were associated with childhood asthma. Compared with children with less ETS exposure (0-5 cigarettes/day) and the CDH1 CC genotype, those with less ETS exposure and the CDH1 AA/CA genotypes and those with more ETS exposure and the CDH1 CC genotype had a moderate risk of asthma. The greatest risk for asthma was in children with more ETS exposure and the CDH1 AA/CA genotypes (OR, 3.03; 95% CI, 1.81-5.06), and this interaction between CDH1 polymorphism and ETS exposure was significant. In addition, asthma cases with more ETS exposure or the CDH1 AA/CA genotypes had obviously increased eosinophil counts. CONCLUSION Susceptible CDH1 genotypes might modulate the development of asthma, especially for children exposed to ETS.
Collapse
Affiliation(s)
- Ming-Fuu Wang
- Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, Tungs' Taichung Metroharbor Hospital, Taichung, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Rehabilitation, Jen-Teh Junior College of Medicine, Nursing, and Management, Miaoli County, Taiwan
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
40
|
Grunnet M, Mau-Sørensen M, Brünner N. Tissue inhibitor of metalloproteinase 1 (TIMP-1) as a biomarker in gastric cancer: a review. Scand J Gastroenterol 2013; 48:899-905. [PMID: 23834019 DOI: 10.3109/00365521.2013.812235] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE The value of Tissue Inhibitor of MetalloProteinase-1 (TIMP-1) as a biomarker in patients with gastric cancer (GC) is widely debated. The aim of this review is to evaluate available literature describing the association between levels of TIMP-1 in tumor tissue and/or blood and the prognosis of patients suffering from GC. MATERIAL AND METHODS Using the search words 'TIMP-1', 'Gastric Cancer' and 'Tumor marker', a search was carried out on PubMed. Exclusion criteria were articles never published in English, articles from before 1995 and articles evaluating tumor markers other than TIMP-1 in GC. RESULTS Of initially 50 articles, 17 were found to fulfill the selection criteria and relevant for this study. The 17 articles evaluated the usefulness of TIMP-1 levels in tumor tissue or blood, respectively, as a prognostic marker in patients with GC. CONCLUSIONS A literature search showed that elevated protein levels of TIMP-1 in either tumor tissue extracts or in plasma from patients suffering from GC associates with poor patient outcome.
Collapse
Affiliation(s)
- Mie Grunnet
- Department of Oncology, Rigshospitalet, Copenhagen, Denmark.
| | | | | |
Collapse
|
|
41
|
Wu J, Guan X, Zhang K, Li YT, Bai P, Wu J. A/G polymorphism of matrix metalloproteinase 7 gene promoter region and cancer risk: A meta-analysis. Biomed Rep 2013; 1:792-796. [PMID: 24649030 DOI: 10.3892/br.2013.131] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2013] [Accepted: 07/08/2013] [Indexed: 01/10/2023] Open
Abstract
This meta-analysis was conducted to evaluate the effect of the matrix metalloproteinase 7 (MMP7)-181A/G polymorphism on cancer risk. Twenty-seven case-control studies were identified via a literature search through PubMed, Web of Science and China National Knowledge Infrastructure databases. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were applied to assess the strength of the association between MMP7-181A/G polymorphism and cancer risk. The 27 studies were further assessed according to Hardy-Weinberg equilibrium (HWE) and Hardy-Weinberg disequilibrium (HWD), with 24 case-control studies found to be under HWE. A significant association was observed between MMP7-181A/G polymorphism and increased cancer risk (cervical and other types of cancer) in Asian, but not in European populations.
Collapse
Affiliation(s)
- Jing Wu
- Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Xuan Guan
- School of Basic Medical Sciences, Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China
| | - Kui Zhang
- Laboratory of Molecular Translational Medicine, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Ya-Ting Li
- Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Peng Bai
- Laboratory of Molecular Translational Medicine, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| | - Jin Wu
- Department of Forensic Biology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China
| |
Collapse
|
|
42
|
Pereza N, Volk M, Zrakić N, Kapović M, Peterlin B, Ostojić S. Genetic variation in tissue inhibitors of metalloproteinases as a risk factor for idiopathic recurrent spontaneous abortion. Fertil Steril 2013; 99:1923-9. [PMID: 23472946 DOI: 10.1016/j.fertnstert.2013.02.018] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2012] [Revised: 02/08/2013] [Accepted: 02/08/2013] [Indexed: 10/27/2022]
Abstract
OBJECTIVE To investigate the potential association of tissue inhibitor of metalloproteinases (TIMP) 1, 2, 3, and 4 gene polymorphisms with idiopathic recurrent spontaneous abortion (IRSA). DESIGN Case-control and association study. SETTING Departments of gynecology and obstetrics and university-based research laboratory. PATIENT(S) A total of 149 couples with a history of three or more idiopathic spontaneous pregnancy losses and 149 fertile men and 149 fertile women with at least two live births and no history of pregnancy pathologies. INTERVENTION(S) Polymerase chain reaction and restriction-fragment-length polymorphism methods. MAIN OUTCOME MEASURE(S) Detection of TIMP-1 -372 C/T, TIMP-2 -303 C/T, TIMP-3 -915 A/G, TIMP-3 -1296 C/T, and TIMP-4 -3'-UTR C/T genotypes and allele frequencies. RESULT(S) There were no statistically significant differences in the distribution of any genotype and allele frequencies or any genetic model between IRSA patients and controls. Additionally, no significant associations occurred between combinations of TIMP polymorphisms and the risk of IRSA. CONCLUSION(S) We found no evidence for the association of TIMP-1, -2, -3, and -4 with IRSA in a Slovenian population.
Collapse
Affiliation(s)
- Nina Pereza
- Department of Biology and Medical Genetics, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | | | | | | | | | | |
Collapse
|
|
43
|
Yang X, Liu Y, Yang Y, Li B. Update meta-analysis on MMP-7 −181A>G polymorphism and cancer risk: Evidence from 25 studies. Gene 2013; 521:252-8. [DOI: 10.1016/j.gene.2013.03.079] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2012] [Revised: 02/25/2013] [Accepted: 03/15/2013] [Indexed: 11/30/2022]
|
|
44
|
Ke P, Wu ZD, Wen HS, Ying MX, Long HC, Qing LG. Current Evidence on Associations Between the MMP-7 (-181A>G) Polymorphism and Digestive System Cancer Risk. Asian Pac J Cancer Prev 2013; 14:2269-72. [DOI: 10.7314/apjcp.2013.14.4.2269] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
|
|
45
|
Vihinen P, Ala-Aho R, Kähäri VM. Diagnostic and prognostic role of matrix metalloproteases in cancer. ACTA ACUST UNITED AC 2013; 2:1025-39. [PMID: 23495924 DOI: 10.1517/17530059.2.9.1025] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
BACKGROUND Matrix metalloproteases (MMPs) are key players in the progression and metastasis of cancer. MMPs cleave extracellular matrix components and in this way promote tumor growth, invasion and vascularization. MMPs also affect tumor progression by regulating availability and activity of growth factors, inflammatory cytokines and chemokines. Accordingly, several MMPs have been found to serve as prognostic indicators in solid tumors. Usually the increased levels of MMPs in patients' tumor tissue or serum/plasma are associated with poor outcome. Interestingly, recent results show that certain MMPs also serve as tumor suppressors. OBJECTIVE This review discusses the latest view on MMPs as diagnostic and prognostic indicators in cancer patients. METHODS Studies with clinical samples of 70 or more patients are included in particular. In addition, the possible roles of MMPs in future molecular diagnostics and in the evaluation of therapeutic responses are discussed. CONCLUSION MMP-9 in particular has shown prognostic value in various types of tumor, and its measurement in circulation, urine or tumor tissue might help in clinical surveillance of otherwise problematic patient cases. There is upcoming new knowledge on MMPs in therapy response evaluation, in which MMPs might be useful together with CT scans and other clinically more established prognostic factors. Certain MMPs have a dual role in terms of cancer-modulating properties and thus it is essential to evaluate their expression and function in tumor cells and host environment to select validated therapy targets but spare MMP antitargets.
Collapse
Affiliation(s)
- Pia Vihinen
- Turku University Hospital, Department of Oncology and Radiotherapy, POB 52, FIN-20521 Turku, Finland +358 2 313 0804 ; +358 2 313 2809 ;
| | | | | |
Collapse
|
|
46
|
Sharma KL, Misra S, Kumar A, Mittal B. Higher risk of matrix metalloproteinase (MMP-2, 7, 9) and tissue inhibitor of metalloproteinase (TIMP-2) genetic variants to gallbladder cancer. Liver Int 2012; 32:1278-1286. [PMID: 22621753 DOI: 10.1111/j.1478-3231.2012.02822.x] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2012] [Revised: 03/24/2012] [Accepted: 04/20/2012] [Indexed: 12/23/2022]
Abstract
BACKGROUND Matrix metalloproteinase belong to family of pericellular collagenases which degrade extracellular matrix (ECM), and is involved in the modulation and susceptibility of various cancers. METHODOLOGY The present study included 410 gallbladder (GBC) cases and 230 healthy controls from North India. Study examined the associations of polymorphisms of MMP-2c.735C>T (rs2285053), MMP-2c.1306 C>T (rs243865), MMP7c.181A>G (rs11568818), MMP-9p.R279Q (rs17556) MMP-9p.P574R (rs2250889), MMP-9 p.R668Q (rs17577) and TIMP2c.418 G>C (rs8179090) to GBC susceptibility. Genotyping was carried out by PCR-RFLP. Statistical analysis was performed by using SPSS ver16. RESULTS The MMP-2 c.735 [CT+TT], MMP-2c.1306 [CT+TT], MMP7 c.181 [AG+GG] and MMP-9 p.668 [RQ+QQ],TIMP2c.418 [GG+GC] genotypes were significantly associated with increased risk of GBC (P = 0.01; [OR]1.87, P = 0.02; [OR] 1.68, P = 0.02; [OR]=1.61, P = 0.002; [OR]=1.91,P = 0.01; [OR]=1.78 and (P = 0.03; [OR]=1.68; P = 0.01; [OR]=1.78 respectively). Haplotypes [C(-735) -T(-1306) ] and [T(-1306) -C(-735) ] of MMP-2 (P = <0.005; [OR] =1.78 P = <0.0001; [OR] =2.09) and haplotype [Q(279) -P(574) -Q(668) ]of the MMP-9 (P = 0.04; [OR] =2.75) were significantly associated with GBC risk. On stratification of GBC patients with/without gallstones, MMP-2 haplotypes were associated with higher GBC risk in patients accompanying gallstones whereas MMP-9 haplotypes showed risk in patients without stones. Combined effect of > 3 MMP/TIMP variant containing genotypes imparted increased risk of GBC (P < 0.0001; [OR] =3.36). Multivariate logistic regression results also supported association of MMP-2 (c.735C>T, c.1306 C>T), MMP-9 p.R668Q and TIMP2c.418G>C variants with GBC susceptibility. CONCLUSION This study suggests that genetic variants in MMP-2,7,9 and TIMP-2genes are associated with higher susceptibility of gallbladder cancer.
Collapse
Affiliation(s)
- Kiran L Sharma
- Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India
| | | | | | | |
Collapse
|
|
47
|
MMP-2 and MMP-9 in normal mucosa are independently associated with outcome of colorectal cancer patients. Br J Cancer 2012; 106:1495-8. [PMID: 22472880 PMCID: PMC3341861 DOI: 10.1038/bjc.2012.80] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Background: Upregulation of the matrix metalloproteinases MMP-2 and MMP-9 in various cancers has been associated with worse survival of the patients. Methods: We assessed MMP-2 and MMP-9 levels in normal colorectal mucosa from colorectal cancer patients in relation to the course of the disease. Results: A high protein expression of MMP-2 as well as MMP-9 in normal mucosa was found to be correlated with worse 5-year survival. The combination of both parameters was an even stronger prognostic factor. These protein levels were found not to be related to the corresponding single nucleotide polymorphisms of MMP-2 (−1306C>T) and MMP-9 (−1562C>T). Multivariate analyses indicated that the MMP-2 and MMP-9 levels in normal mucosa are prognostic for survival, independent of TNM classification. Conclusion: MMP-2 and MMP-9 levels in normal mucosa are indicative of the course of disease in colorectal cancer patients.
Collapse
|
|
48
|
Baren JP, Stewart GD, Stokes A, Gray K, Pennington CJ, O'Neill R, Deans DAC, Paterson-Brown S, Riddick ACP, Edwards DR, Fearon KCH, Ross JA, Skipworth RJE. mRNA profiling of the cancer degradome in oesophago-gastric adenocarcinoma. Br J Cancer 2012; 107:143-9. [PMID: 22677901 PMCID: PMC3389427 DOI: 10.1038/bjc.2012.239] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Background: Degradation of the extracellular matrix is fundamental to tumour development, invasion and metastasis. Several protease families have been implicated in the development of a broad range of tumour types, including oesophago–gastric (OG) adenocarcinoma. The aim of this study was to analyse the expression levels of all core members of the cancer degradome in OG adenocarcinoma and to investigate the relationship between expression levels and tumour/patient variables associated with poor prognosis. Methods: Comprehensive expression profiling of the protease families (matrix metalloproteinases (MMPs), members of the ADAM metalloproteinase-disintegrin family (ADAMs)), their inhibitors (tissue inhibitors of metalloproteinase), and molecules involved in the c-Met signalling pathway, was performed using quantitative real-time reverse transcription polymerase chain reaction in a cohort of matched malignant and benign peri-tumoural OG tissue (n=25 patients). Data were analysed with respect to clinico-pathological variables (tumour stage and grade, age, sex and pre-operative plasma C-reactive protein level). Results: Gene expression of MMP1, 3, 7, 9, 10, 11, 12, 16 and 24 was upregulated by factors >4-fold in OG adenocarcinoma samples compared with matched benign tissue (P<0.01). Expression of ADAM8 and ADAM15 correlated significantly with tumour stage (P=0.048 and P=0.044), and ADAM12 expression correlated with tumour grade (P=0.011). Conclusion: This study represents the first comprehensive quantitative analysis of the expression of proteases and their inhibitors in human OG adenocarcinoma. These findings implicate elevated ADAM8, 12 and 15 mRNA expression as potential prognostic molecular markers.
Collapse
Affiliation(s)
- J P Baren
- Tissue Injury and Repair Group, Clinical and Surgical Sciences, University of Edinburgh-MRC Centre for Regenerative Medicine, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh, UK
| | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
49
|
Yuan-Yuan M, Li-Feng Z, Li-Jie Z. MMP7 −181G Allele Is a Low-Penetrant Risk Factor for Cancer Development in East Asians. DNA Cell Biol 2012; 31:772-6. [PMID: 22047080 DOI: 10.1089/dna.2011.1416] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Affiliation(s)
- Mi Yuan-Yuan
- Department of Urology, Third Affiliated Hospital of Nantong University, Wuxi, China
| | - Zhang Li-Feng
- Department of Urology, Affiliated Changzhou No 2. Hospital of Nanjing Medical University, Changzhou, China
| | - Zhu Li-Jie
- Department of Urology, Third Affiliated Hospital of Nantong University, Wuxi, China
| |
Collapse
|
|
50
|
Krishnaveni D, Bhayal AC, Sri Manjari K, Vidyasagar A, Uma Devi M, Ramanna M, Jyothy A, Nallari P, Venkateshwari A. MMP 9 Gene Promoter Polymorphism in Gastric Cancer. Indian J Clin Biochem 2012; 27:259-64. [PMID: 26405384 DOI: 10.1007/s12291-012-0210-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2012] [Accepted: 03/26/2012] [Indexed: 12/16/2022]
Abstract
Matrix metalloproteinase-9 (gelatinase B) plays a key role in cancer invasion and metastasis by degrading the extracellular matrix and basement membrane barriers. A cytosine (C) > thymidine (T) single nucleotide polymorphism (SNP) at position -1562 in the MMP-9 promoter is reported to influence the expression of the gene. Genotyping of MMP-9 -1562 C→T promoter polymorphism in 140 gastric cancer patients and 132 healthy control subjects was carried out in order to evaluate its association with progression and development of gastric cancer. The SNP was genotyped by tetra-primer amplification refractory mutation system-polymerase chain reaction followed by agarose gel electrophoresis. Statistical methods were adopted to test for the significance of the results. Risk factor profile of the patients revealed age above 50 years, smoking, alcoholism as the factors associated with the disease. The distribution of genotype frequencies in gastric cancer patients were 28.7 % of CC, 45.5 % of CT and 25.7 % of TT, whereas in control subjects 31.8 % of CC, 53.03 % of CT and 15.15 % of TT, respectively. The allelic frequencies were 51.51 % of C and 48.48 % of T in patient group and 58.33 % of C and 41.66 % of T in controls respectively. The present study shows the possible association of epidemiological risk factors with gastric cancer. There is an increased frequency of T allele in the disease compared to control subjects. However, there is no association of the MMP-9 -1562 C→T promoter polymorphism in the development of gastric cancer.
Collapse
Affiliation(s)
- D Krishnaveni
- Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad, 500 016 India
| | - Amar Chand Bhayal
- Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad, 500 016 India
| | - K Sri Manjari
- Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad, 500 016 India
| | - A Vidyasagar
- Department of Gastroenterology, Gandhi Hospital, Hyderabad, 500 003 India
| | - M Uma Devi
- Department of Gastroenterology, Gandhi Hospital, Hyderabad, 500 003 India
| | - M Ramanna
- Department of Gastroenterology, Gandhi Hospital, Hyderabad, 500 003 India
| | - A Jyothy
- Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad, 500 016 India
| | - Pratibha Nallari
- Department of Genetics, Osmania University, Hyderabad, 500 007 India
| | - A Venkateshwari
- Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad, 500 016 India
| |
Collapse
|