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Liu BX, Xie Y, Zhang J, Zeng S, Li J, Tao Q, Yang J, Chen Y, Zeng C. SERPINB5 promotes colorectal cancer invasion and migration by promoting EMT and angiogenesis via the TNF-α/NF-κB pathway. Int Immunopharmacol 2024; 131:111759. [PMID: 38460302 DOI: 10.1016/j.intimp.2024.111759] [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] [Received: 11/06/2023] [Revised: 02/20/2024] [Accepted: 02/22/2024] [Indexed: 03/11/2024]
Abstract
This study aimed to investigate the role of SERPINB5 in colorectal cancer (CRC). We established knockdown and overexpression models of SERPINB5 in CRC cells and conducted bioinformatics analysis to assess the clinicopathological significance of SERPINB5 expression in CRC patients. Human CRC cells were transfected with LV-SERPINB5 and sh-SERPINB5 lentivirus for subsequent functional and mechanistic studies. Results showed that high SERPINB5 expression correlated positively with CEA levels, N stage and lymphatic infiltration, while displaying a negative correlation with progression-free survival. Overexpression of SERPINB5 in CRC cells upregulated the expression of TNF-α, p-NF-κB/p65, N-cadherin, MMP2 and MMP9, accompanied by decreased E-cadherin expression. In addition, SERPINB5 overexpression enhanced the migration, invasion, and proliferation of CRC cells. Furthermore, overexpression of SERPINB5 in CRC cells increased VEGFA expression, and the conditioned medium from SERPINB5-overexpressing CRC cells promoted tube formation of HUVECs. Conversely, overexpression of SERPINB5 in HUVECs decreased VEGFA expression and inhibited tube formation. Notably, these changes in CRC cells were reversed by QNZ, a specific inhibitor of the TNF-α/NF-κB pathway. In summary, our findings revealed that high SERPINB5 expression correlated with poor progression-free survival in CRC patients. Moreover, SERPINB5 could induce EMT and angiogenesis by activating the TNF-α/NF-κB pathway, thereby promoting the invasion and migration of CRC cells.
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Affiliation(s)
- Bi-Xia Liu
- Department of Gastroenterology, Digestive Disease Hospital, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 17 Yongwaizheng Street, Nanchang 330000, Jiangxi, China; Department of Gastroenterology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330000, Jiangxi, China
| | - Yang Xie
- Department of Gastroenterology, Digestive Disease Hospital, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 17 Yongwaizheng Street, Nanchang 330000, Jiangxi, China
| | - Jiayu Zhang
- Huankui Academy of Nanchang University, Nanchang 330000, Jiangxi, China
| | - Shuyan Zeng
- Huankui Academy of Nanchang University, Nanchang 330000, Jiangxi, China
| | - Jun Li
- Department of Gastroenterology, Digestive Disease Hospital, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 17 Yongwaizheng Street, Nanchang 330000, Jiangxi, China
| | - Qing Tao
- Department of Gastroenterology, Digestive Disease Hospital, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 17 Yongwaizheng Street, Nanchang 330000, Jiangxi, China
| | - Jing Yang
- Department of Gastroenterology, Digestive Disease Hospital, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 17 Yongwaizheng Street, Nanchang 330000, Jiangxi, China
| | - Youxiang Chen
- Department of Gastroenterology, Digestive Disease Hospital, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 17 Yongwaizheng Street, Nanchang 330000, Jiangxi, China
| | - Chunyan Zeng
- Department of Gastroenterology, Digestive Disease Hospital, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 17 Yongwaizheng Street, Nanchang 330000, Jiangxi, China; Jiangxi Provincial Key Laboratory of Interdisciplinary Science, Nanchang University, Nanchang 330000, Jiangxi, China.
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Shi S, Zhang ZG, Sang YZ, Sun J, Ma HY. A meta‑ and bioinformatics analysis of maspin expression levels influencing the prognosis of patients with breast cancer. Oncol Lett 2024; 27:173. [PMID: 38464336 PMCID: PMC10921733 DOI: 10.3892/ol.2024.14306] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 02/06/2024] [Indexed: 03/12/2024] Open
Abstract
Maspin is a serine protease inhibitor that is encoded by the human SERPINB5 gene. As a tumor inhibitor, it can inhibit the growth of tumor cells, increase adhesion between tumor cells and inhibit tumor angiogenesis. In the present study, a meta- and bioinformatics analysis was performed through the PubMed and China National Knowledge Infrastructure databases including entries added until up to March 20, 2023. It was found that compared with normal breast tissue, maspin expression was downregulated in breast cancer tissue. Maspin expression was negatively associated with lymph node metastasis. According to Kaplan-Meier plotter, it was found that lower maspin expression was negatively associated with the overall and distant metastasis-free survival rate of patients with estrogen receptor-positive, luminal A and grade 2 breast cancer. High expression of maspin was also positively associated with the relapse-free survival rate of patients of the luminal A subtype. Low maspin expression was positively associated with the post-progression and distant metastasis-free survival rate of the progesterone receptor-negative subtype. According to the GEPIA database, SERPINB5 mRNA expression was higher in normal than breast cancer tissues and negatively correlated with the TNM stage. High expression of maspin was also positively associated with the overall survival rate. In the UALCAN database, it was found that the mRNA and promoter methylation levels of SERPINB5 were higher in normal than in breast cancer tissues. These findings suggest that the expression of maspin may serve as a potential marker to indicate the occurrence, subsequent progression and even prognosis of breast cancer.
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Affiliation(s)
- Shuai Shi
- Department of Pathology, Cangzhou People's Hospital,
Cangzhou, Hebei 061000, P.R. China
| | - Zhi-Gang Zhang
- Department of Pathology, Cangzhou People's Hospital,
Cangzhou, Hebei 061000, P.R. China
| | - Yin-Zhou Sang
- Department of Pathology, Cangzhou People's Hospital,
Cangzhou, Hebei 061000, P.R. China
| | - Jie Sun
- Department of Pathology, Cangzhou People's Hospital,
Cangzhou, Hebei 061000, P.R. China
| | - Hong-Yan Ma
- Department of Pathology, Cangzhou People's Hospital,
Cangzhou, Hebei 061000, P.R. China
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Wakahara M, Hosoya K, Ishii H, Umekita Y. Clinical Significance of Subcellular Localization of Maspin in Breast Carcinoma: An Immunohistochemical Study Using Two Different Antibodies. Yonago Acta Med 2023; 66:19-23. [PMID: 36820287 PMCID: PMC9937968 DOI: 10.33160/yam.2023.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 11/28/2022] [Indexed: 01/17/2023]
Abstract
Background Maspin is known to be a tumor suppressor protein: however, its prognostic value in patients with breast cancer remains controversial. The key influential factors contributing to this complexity may be the differences in antibodies used, as well as the positive criteria and sample size. To date, no study has investigated the prognostic significance of maspin expression by using two different antibodies in the same cohort. We aimed to clarify whether differences in antibodies could influence on the prognostic value of maspin in breast cancer patients. Methods Immunohistochemical analyses using an anti-maspin antibody (clone G167-70) were performed on 164 resected specimens of invasive carcinoma of no special type (NOS). The correlation with clinicopathological factors was compared to previous results using clone EAW24, with longer follow-up duration. Results The subcellular localization of maspin expression was as follows: cytoplasmic-only staining, 3 cases (1.8%), pancellular staining, 43 cases (26.2%); and no staining, 118 cases (72.0%). No nuclear-only staining was observed. There was no significant correlation between clinicopathological characteristics and the pancellualr expression of maspin. The pancellular expression group showed a significantly longer disease-free survival (DFS) than the other groups (P = 0.046). When clone EAW24 was used, the cytoplasmic-only staining group showed significantly shorter DFS than the pancellular staining group (P = 0.003). Conclusion Clone EAW24 may be superior to clone G167-70 in selecting breast carcinoma with an aggressive phenotype, while clone G167-70 may be superior to clone EAW24 in selecting non-aggressive breast carcinoma.
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Affiliation(s)
- Makoto Wakahara
- Division of General Thoracic Surgery and Breast and Endocrine Surgery, Department of Surgery, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan
| | - Keiko Hosoya
- Division of General Thoracic Surgery and Breast and Endocrine Surgery, Department of Surgery, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan,Department of Pathology, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan
| | - Hiroshi Ishii
- Department of Pathology, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan
| | - Yoshihisa Umekita
- Department of Pathology, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8503, Japan
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Tang S, Ling Z, Jiang J, Gu X, Leng Y, Wei C, Cheng H, Li X. Integrating the tumor-suppressive activity of Maspin with p53 in retuning the epithelial homeostasis: A working hypothesis and applicable prospects. Front Oncol 2022; 12:1037794. [PMID: 36523976 PMCID: PMC9745138 DOI: 10.3389/fonc.2022.1037794] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Accepted: 11/10/2022] [Indexed: 12/20/2024] Open
Abstract
Epithelial malignant transformation and tumorous development were believed to be closely associated with the loss of its microenvironment integrity and homeostasis. The tumor-suppressive molecules Maspin and p53 were demonstrated to play a crucial role in body epithelial and immune homeostasis. Downregulation of Maspin and mutation of p53 were frequently associated with malignant transformation and poor prognosis in various human cancers. In this review, we focused on summarizing the progress of the molecular network of Maspin in studying epithelial tumorous development and its response to clinic treatment and try to clarify the underlying antitumor mechanism. Notably, Maspin expression was reported to be transcriptionally activated by p53, and the transcriptional activity of p53 was demonstrated to be enhanced by its acetylation through inhibition of HDAC1. As an endogenous inhibitor of HDAC1, Maspin possibly potentiates the transcriptional activity of p53 by acetylating the p53 protein. Hereby, it could form a "self-propelling" antitumor mechanism. Thus, we summarized that, upon stimulation of cellular stress and by integrating with p53, the aroused Maspin played the epigenetic surveillant role to prevent the epithelial digressional process and retune the epithelial homeostasis, which is involved in activating host immune surveillance, regulating the inflammatory factors, and fine-tuning its associated cell signaling pathways. Consequentially, in a normal physiological condition, activation of the above "self-propelling" antitumor mechanism of Maspin and p53 could reduce cellular stress (e.g., chronic infection/inflammation, oxidative stress, transformation) effectively and achieve cancer prevention. Meanwhile, designing a strategy of mimicking Maspin's epigenetic regulation activity with integrating p53 tumor-suppressive activity could enhance the chemotherapy efficacy theoretically in a pathological condition of cancer.
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Affiliation(s)
- Sijie Tang
- Department of Urology, Affiliated Aoyang Hospital of Jiangsu University, Zhangjiagang, Suzhou, China
- Aoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu University, Zhangjiagang, Suzhou, China
| | - Zhongli Ling
- Department of Urology, Affiliated Aoyang Hospital of Jiangsu University, Zhangjiagang, Suzhou, China
| | - Jiajia Jiang
- Aoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu University, Zhangjiagang, Suzhou, China
| | - Xiang Gu
- Department of Urology, Affiliated Aoyang Hospital of Jiangsu University, Zhangjiagang, Suzhou, China
| | - Yuzhong Leng
- Department of Urology, Affiliated Aoyang Hospital of Jiangsu University, Zhangjiagang, Suzhou, China
| | - Chaohui Wei
- Department of Urology, Affiliated Aoyang Hospital of Jiangsu University, Zhangjiagang, Suzhou, China
| | - Huiying Cheng
- Aoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu University, Zhangjiagang, Suzhou, China
| | - Xiaohua Li
- Aoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu University, Zhangjiagang, Suzhou, China
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ElEsawy Y, Khaled E, Biomy B, Elsheikh S, El-Yasergy D. The Role of Maspin Expression as Diagnostic Tissue Marker in Pancreaticoduodenal Malignant Tumors and Benign Lesions. Open Access Maced J Med Sci 2022. [DOI: 10.3889/oamjms.2022.9765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND: Maspin (a tumor suppressor gene) is down-regulated in breast, prostate, gastric, and melanoma. Although it is not detected in normal pancreatic tissue, it is over-expressed in pancreatic cancer suggesting that maspin may play different activities in different cell types. Pancreatic ductal adenocarcinoma (PC) acquires maspin expression through hypomethylation of its promoter.
AIM: Because the discrimination between ampullary and periampullary carcinomas is challenging in advanced cases, this inspired us to search for the use of maspin expression to discriminate between ampullary carcinoma (AC), PC, duodenal adenocarcinoma (DC), and other confusing benign and inflammatory pancreatic lesions.
METHODS: Immunostaining for maspin was performed for 80 pancreaticoduodenal lesions. Sixty cases were malignant: 48 cases of pancreatic epithelial tumor (41 PC and 7 solid pseudopapillary neoplasm), 9 AC, and 3 DC. Twenty cases were non-malignant: 12 inflammatory (chronic pancreatitis), 5 benign neoplastic (serous cystadenomas), and 3 normal pancreatic tissue. Cytoplasmic and/or nuclear staining was considered positive as: Focally positive (5–50% of tumor cells), diffusely positive (>50% of tumor cells), or negative (<5% tumor cells).
RESULTS: Maspin expression (positive/negative), distribution (focal/diffuse), and nuclear expression are significantly different between PC, solid pseudopapillary neoplasm, AC, and DC. PC shows significantly higher expression with more diffuse positivity and more nuclear expression than other malignant groups. Forty cases of PC (40/41) (97.6%) showed positive expression; 28 of them (28/40) (70%) showed diffuse expression and 82.5% (33 cases) showed nuclear and cytoplasmic expression. Only one case (14.3%) (1/7) of solid pseudopapillary neoplasm showed positive focal cytoplasmic expression. Three AC cases (3/9) (33.3%) showed positive focal cytoplasmic expression. Two cases of DC (2/3) (66.7%) showed positive focal cytoplasmic expression. Maspin expression shows significant positive correlation with poor prognostic variables as tumor grade, lymphovascular invasion, T stage of PC. Minority of chronic pancreatitis and benign lesions are maspin positive with significant difference from the malignant groups.
CONCLUSION: Our results suggest that maspin can be of value in differentiating pancreatic adenocarcinoma from ampullary carcinoma, duodenal adenocarcinoma, and other confusing lesions as chronic pancreatitis.
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Khorsandi L, Farasat M. Zinc oxide nanoparticles enhance expression of maspin in human breast cancer cells. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2020; 27:38300-38310. [PMID: 32621200 DOI: 10.1007/s11356-020-09986-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Accepted: 07/01/2020] [Indexed: 06/11/2023]
Abstract
Toxic and apoptotic impacts of zinc oxide nanoparticle (ZNP) on different cancer cells have been reported. Maspin (a mammary serine protease inhibitor) as a tumor suppressor gene can inhibit tumor growth and metastasis. The expression of maspin is modulated by p53, Bcl-2 family genes, and estrogen receptor α (ER-α). This study aimed to assess the ZNP effects on maspin expression in MCF-7 cells (a breast cancer cell). Experimental groups (ZNP5, ZNP10, and ZNP20) received 5, 10, and 20 μM/mL ZNP for 48 h, respectively. 17-β-estradiol (E2) was used to evaluate the role of ER-α in the anticancer impact of ZNP. Cell viability, Annexin V, migration assay, gene expression, and western blotting methods were applied to evaluate ZNP effects on the MCF-7 cells. ZNP at the concentrations of 10 and 20 μM/mL could significantly decrease the viability and migration rate, and significantly increase apoptosis percentage in the MCF-7 cells. ZNP significantly enhanced mRNA expression and protein level of maspin in MCF-7 cells in a concentration-dependent way. ZNP concentration-dependently elevated mRNA expression and protein level of p53 and Bax while reduced the expression of Bcl-2 and ER-α. E2 promoted cancer cell growth by enhancing survival and migration rates. E2 treatment reduced mRNA expression and protein level of maspin and p53, and elevated Bcl-2 expression. ZNP considerably changed these events induced by E2 in the MCF-7 cells. It is concluded that the maspin overexpression is one of the toxic mechanisms of the ZNP on the ER-α-positive breast cancer cells, and can suppress the migration of these cells.
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Affiliation(s)
- Layasadat Khorsandi
- Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
- Department of Anatomical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
| | - Maryam Farasat
- Department of Anatomical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Banias L, Jung I, Gurzu S. Subcellular expression of maspin – from normal tissue to tumor cells. World J Meta-Anal 2019; 7:142-155. [DOI: 10.13105/wjma.v7.i4.142] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2019] [Revised: 04/22/2019] [Accepted: 04/23/2019] [Indexed: 02/06/2023] Open
Abstract
Maspin or SerpinB5, a member of the serine protease inhibitor family, was shown to function as a tumor suppressor, especially in carcinomas. It seems to inhibit invasion, tumor cells motility and angiogenesis, and promotes apoptosis. Maspin can also induce epigenetic changes such as cytosine methylation, de-acetylation, chromatin condensation, and histone modulation. In this review, a comprehensive synthesis of the literature was done to present maspin function from normal tissues to pathologic conditions. Data was sourced from MEDLINE and PubMed. Study eligibility criteria included: Published in English, between 1994 and 2019, specific to humans, and with full-text availability. Most of the 118 studies included in the present review focused on maspin immunostaining and mRNA levels. It was shown that maspin function is organ-related and depends on its subcellular localization. In malignant tumors, it might be downregulated or negative (e.g., carcinoma of prostate, stomach, and breast) or upregulated (e.g., colorectal and pancreatic tumors). Its subcellular localization (nuclear vs cytoplasm), which can be proved using immunohistochemical methods, was shown to influence both tumor behavior and response to chemotherapy. Although the number of maspin-related papers increased, the exact role of this protein remains unknown, and its interpretation should be done with extremely high caution.
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Affiliation(s)
- Laura Banias
- Department of Pathology, University of Medicine, Pharmacy, Sciences and Technology of Tirgu-Mures, Tirgu Mures 540139, Romania
- Department of Pathology, Clinical County Emergency Hospital, Tirgu Mures 540139, Romania
| | - Ioan Jung
- Department of Pathology, University of Medicine, Pharmacy, Sciences and Technology of Tirgu-Mures, Tirgu Mures 540139, Romania
| | - Simona Gurzu
- Department of Pathology, University of Medicine, Pharmacy, Sciences and Technology of Tirgu-Mures, Tirgu Mures 540139, Romania
- Department of Pathology, Clinical County Emergency Hospital, Tirgu Mures 540139, Romania
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Hardika AS, Fauziah D. Analysis of Maspin Expression in Invasive Ductal Carcinoma of the Breast on Stages IIA and IIIB. FOLIA MEDICA INDONESIANA 2018. [DOI: 10.20473/fmi.v54i1.8043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Mammary Serine Protease Inhibitor (maspin) is a tumor suppressor gene, a member of the serine protease inhibitor (serpin) family that works by inhibiting motility of cell movement, invasion and metastasis. Maspin expression is expected to be a prognostic factor as well as a predictive factor in mammary tumors. However, in some recent studies, maspin has a variety of expressions. Although it is known that no maspine appears as an indicator of tumor progression and metastasis, recent study has shown that maspine expression is associated with an aggressive phenotype of breast cancer and with a poor prognosis. Correlations between maspine expression and poor prognosis have also been reported in pancreatic, ovarian, thyroid, bladder and lung cancers. Knowledge of the expression and role of this maspin as well as its relationship with the pathogenesis of breast invasive ductal carcinoma is still small. The aim of this study was to look at differences in maspin expression in breast-invasive ductal carcinoma of stage IIA and stage IIIB groups. This research method used analytic observational research with cross sectional approach. The samples were invasive carcinoma of NST paraffin at the Department of Anatomic Pathology of Dr Soetomo Hospital, Surabaya, from January to December 2015. Thirty samples were divided into two groups, namely stage IIA and stage IIIB groups and immunohistochemical examination with maspin antibody was carried out. The difference of maspin expression in stage IIA and stage IIIB was analyzed using Mann-Whitney statistic test. There were significant differences in maspin expression between stage IIA and stage IIIB groups, where stage IIA has a high maspin expression rather than stage IIIB.
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Helal DS, El-Guindy DM. Maspin expression and subcellular localization in invasive ductal carcinoma of the breast: Prognostic significance and relation to microvessel density. J Egypt Natl Canc Inst 2017; 29:177-183. [PMID: 29126758 DOI: 10.1016/j.jnci.2017.09.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2017] [Revised: 09/27/2017] [Accepted: 09/28/2017] [Indexed: 12/20/2022] Open
Abstract
Maspin (Mammary serine protease inhibitor) is a tumor suppressor serine. Its clinical significance and role in breast carcinoma are contradictory and inconclusive. Researches demonstrated that the function of maspin differs according to its subcellular localization. This study was conducted to investigate the expression of maspin in invasive ductal carcinoma (IDC) of the breast with special emphasis on its subcellular localization and to evaluate its prognostic role in relation to clinicopathological parameters and microvessel density (MVD) of the tumor. The expression of maspin was evaluated immunohistochemically in 45 IDC cases. The positive rate of maspin expression was 73.3%. Maspin positivity was significantly related to higher tumor grade (p value = 0.041), nodal metastasis (p value = 0.044), perineural invasion (p value = 0.047), and high CD34+MVD (p value = 0.002). Nuclear maspin was detected in 36.6% whereas cytoplasmic maspin was detected in 63.4% of maspin positive cases. A significant inverse relationship was observed between nuclear maspin and high tumor grade (p value = 0.016), and nodal metastasis (p value = 0.047). These results suggest that maspin expression has a prognostic role in breast cancer. Maspin expression is related to increased angiogenesis. Subcellular localization of maspin can strongly affect cancer prognosis. Cytoplasmic maspin relates to poor prognostic parameters whereas nuclear maspin relates to good prognostic ones.
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Affiliation(s)
- Duaa S Helal
- Pathology Department, Faculty of Medicine, Tanta University, Egypt
| | - Dina M El-Guindy
- Pathology Department, Faculty of Medicine, Tanta University, Egypt.
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Bernardo MM, Dzinic SH, Matta MJ, Dean I, Saker L, Sheng S. The Opportunity of Precision Medicine for Breast Cancer With Context-Sensitive Tumor Suppressor Maspin. J Cell Biochem 2017; 118:1639-1647. [PMID: 28262971 DOI: 10.1002/jcb.25969] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2017] [Accepted: 03/01/2017] [Indexed: 12/12/2022]
Abstract
To improve the precision of molecular diagnosis and to develop and guide targeted therapies of breast cancer, it is essential to determine the mechanisms that underlie the specific tumor phenotypes. To this end, the application of a snapshot of gene expression profile for breast cancer diagnosis and prognosis is fundamentally challenged since the tissue-based data are derived from heterogonous cell types and are not likely to reflect the dynamics of context-dependent tumor progression and drug sensitivity. The intricate network of epithelial differentiation program can be concertedly controlled by tumor suppressor maspin, a homologue of clade B serine protease inhibitors (serpin), through its multifaceted molecular interactions in multiple subcellular localizations. Unlike most other serpins that are expressed in multiple cell types, maspin is epithelial specific and has distinct roles in luminal and myoepithelial cells. Endogenously expressed maspin has been found in the nucleus and cytoplasm, and detected on the surface of cell membrane. It is also secreted free and as an exosomal cargo protein. Research in the field has led to the identification of the maspin targets and maspin-associated molecules, as well as the structural determinants of its suppressive functions. The current review discusses the possibility for maspin to serve as a cell type-specific and context-sensitive marker to improve the precision of breast cancer diagnosis and prognosis. These advancements further suggest a new window of opportunity for designing novel maspin-based chemotherapeutic agents with improved anti-cancer potency. J. Cell. Biochem. 118: 1639-1647, 2017. © 2017 Wiley Periodicals, Inc.
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Affiliation(s)
- Margarida M Bernardo
- Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit 48201, Michigan
| | - Sijana H Dzinic
- Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit 48201, Michigan
| | - Maria J Matta
- Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit 48201, Michigan
| | - Ivory Dean
- Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit 48201, Michigan
| | - Lina Saker
- Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit 48201, Michigan
| | - Shijie Sheng
- Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit 48201, Michigan
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Dabiri S, Moeini Aghtaei M, Shahryari J, Shamis Meymandi M, Amirpour-Rostami S, Foutohi Ardekani R. Maspin Gene Expression in Invasive Ductal Carcinoma of Breast. IRANIAN JOURNAL OF PATHOLOGY 2016; 11:104-111. [PMID: 27499770 PMCID: PMC4939639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 02/04/2015] [Accepted: 10/10/2015] [Indexed: 06/06/2023]
Abstract
BACKGROUND The breast cancer is the most prevalent cancer among women, on the other hand absence of myoepithelial cells play a pivotal role in pathogenesis of this cancer. Thus we aimed to investigate the possible abilities of the molecular assay technique to find a relationship between mammary serine protease inhibitor (Maspin) gene expression possibly secreted by myoepithelial cells, grade of breast cancer and other prognostics factors (ER, PR, and c-erb-B2). METHODS Paraffin embedded blocks of 31 breast cancer patients together with two normal breast tissues were used for IHC staining and Maspin gene RNA detection uses the real-time PCR method. Applying QIAGEN kit, we were able to measure Maspin RNA and Extract the cDNA of different samples for evaluating the Maspin RNA level. RESULTS We found that the RNA level was considerably lowerin these cancer samples compared with normal samples. In addition, different grades of breast cancer in the obtained results adopt some distinguishable values. The Maspin expression in samples with grades II and III is much lower than the ones in normal group (P<0.05) which could be considered as a promising way in diagnosing of this disease. The results showed no considerable differences in Maspin gene expression of the c-erb-B2 scores in the tumor group except the samples having score 0. The other observation of this research study confirmed that Maspin gene expression couldn't show any differences between the values of both ER and PR in different scores of the tumor group. On the other hand, the cDNA of these patients showed lower values compared with normal samples. CONCLUSION Maspin expression was reduced in samples with grade II& III of invasive ductal carcinoma. Based on expression of Maspin Inc-erb-B2, it seems that more expression happened in normal group comparing with different scores of it. We could suggest that there was a reverse relationship between tumor formation and Maspin gene expression. These results showed possible role of Maspin as prognostic factor.
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Affiliation(s)
- Shahriar Dabiri
- Pathology and Stem cell research center,Pathology Department, Afzalipour Medical School, Kerman University of Medical Science, Kerman, Iran
| | - Mohammadmehdi Moeini Aghtaei
- Pathology and Stem cell research center,Pathology Department, Afzalipour Medical School, Kerman University of Medical Science, Kerman, Iran
| | - Jahanbano Shahryari
- Pathology and Stem cell research center,Pathology Department, Afzalipour Medical School, Kerman University of Medical Science, Kerman, Iran
| | - Manzume Shamis Meymandi
- Dept. of Pharmacology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Sahar Amirpour-Rostami
- Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Reza Foutohi Ardekani
- Molecular and Medicine Research Center, Arak University of Medical Sciences, Arak, Iran
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Expression and localization of maspin in cervical cancer and its role in tumor progression and lymphangiogenesis. Arch Gynecol Obstet 2014; 289:373-82. [PMID: 23959090 PMCID: PMC3894428 DOI: 10.1007/s00404-013-2988-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2013] [Accepted: 07/26/2013] [Indexed: 12/14/2022]
Abstract
Objectives Cervical cancer is the most common malignant tumor in female reproductive tract and primarily metastasizes through the lymphatic system that will affect prognosis of patients. Maspin, a member of the serine protease inhibitors (serpins) super family, has recently been indicated as a tumor suppressor in many cancers. In this study, we investigated the clinical significance of maspin expression, especially the subcellular location of maspin and its functional role in progression and lymphangiogenesis, in cervical squamous cell carcinoma. Methods Labelled streptavidin biotin method (LSAB) was used to determine cytoplasmic and nuclear maspin expressions, respectively, in 13 cases of normal cervix, 15 cases of cervical intraepithelial neoplasia grade 3 (CIN3), 62 cases of squamous cell carcinoma (SCC) of the uterine cervix, and 13 cases of pelvic lymphatic nodes which were all positive lymphatic nodes in our selected cancer cases. LSAB is also used to detect podoplanin which is used for counting density of lymphatic microvessels (LMVD). The clinical significance of subcellular maspin expression and the relationship between maspin expression and LMVD in cervical cancer are analyzed. Results Both cytoplasmic and nuclear maspin expressions in SCC were significantly weaker than those of normal cervix and CIN3. Nuclear maspin expression showed a peak in CIN3 and then dropped in SCC. Declined maspin expression was correlated with later clinical stage, increased LMVD, and lymphatic metastasis. Conclusions Our results suggest that subcellular location of maspin expression is a potential predictive factor in tumor progression and in patients’ prognosis of cervical cancer, and maspin plays a suppression role in lymphangiogenesis and metastasis.
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Expression of maspin and ezrin proteins in periocular Basal cell carcinoma. Dermatol Res Pract 2014; 2014:596564. [PMID: 25580109 PMCID: PMC4279255 DOI: 10.1155/2014/596564] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2014] [Accepted: 11/28/2014] [Indexed: 12/04/2022] Open
Abstract
Background. The aim of this study was to investigate maspin and ezrin expression in different subtypes of periocular basal cell carcinoma (BCC). Methods. Tissue samples from 43 patients with periocular BCC. Our cases were comprised of 10 morpheaform, 25 nodular, and 8 adenoid type BCCs. Immunohistochemical staining for maspin and ezrin was performed by Envision detection system. Results. There was no difference between different subtypes of BCC in maspin expression regarding positivity, intensity, and pattern of expression. Ezrin was expressed in all subtypes of BCC but the intensity was significantly higher in morpheaform BCC compared to nodular and adenoid types (P < 0.001 and P = 0.012, resp.); ninety percent of morpheaform samples showed strong ezrin intensity, while this strong intensity was only present in 25% and 12% of adenoid and nodular subtypes, respectively. There was no correlation between age, sex, or tumor margin involvement and expression of neither maspin nor ezrin. There was no correlation between maspin and ezrin expression except in nodular type, in which an inverse correlation was found (P = 0.004). Conclusion. Ezrin is expressed intensely in morpheaform BCC of periocular region. Further studies are needed to show the significance of this finding in prognosis of morpheaform BCC.
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Wang X, Wang Y, Li S, Dong B, Zheng Q, Yan S, Ma Y, Zhang J, Fang J, Wu N, Wu H, Yang Y. Decreased maspin combined with elevated vascular endothelial growth factor C is associated with poor prognosis in non-small cell lung cancer. Thorac Cancer 2014; 5:383-90. [PMID: 26767029 DOI: 10.1111/1759-7714.12104] [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: 01/27/2014] [Accepted: 02/24/2014] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND This study aimed to investigate the clinical significance of the combination of maspin and vascular endothelial growth factor (VEGF)-C expression in the prognosis of non-small cell lung cancer (NSCLC). METHODS Immunohistochemistry was performed to assay the expression of maspin and VEGF-C in primary tumor tissues, metastatic, and non-metastatic lymph nodes in 98 NSCLC patients. Survival analysis was determined by Kaplan-Meier curves. RESULTS The positive expression rate of maspin was 26.5% (26/98) in NSCLC primary tumor tissues, significantly associated with histological type (P = 0.005) and the absence of nodal metastasis (P < 0.001). The expression of maspin in primary tumor tissues was stronger than metastatic lymph nodes of the N1 group (P = 0.048), while the metastatic lymph nodes of the N1 group had a stronger maspin expression than the N2 group (P = 0.008). In survival analysis, a positive expression of maspin of the N1 lymph node was also found to be an independent positive prognostic factor in overall survival (P = 0.003). We also found that decreased maspin combined with elevated VEGF-C is associated with a poor prognosis for disease-free survival (P = 0.019). CONCLUSION Our results suggest that positive expression of maspin might significantly inhibit nodal metastasis in NSCLC. Decreased maspin combined with elevated VEGF-C might be associated with a poor prognosis in NSCLC.
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Affiliation(s)
- Xing Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery, Peking University Cancer Hospital & Institute Beijing, China
| | - Yang Wang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Respiratory Medicine, Peking University Cancer Hospital & Institute Beijing, China
| | - Shaolei Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery, Peking University Cancer Hospital & Institute Beijing, China
| | - Bin Dong
- Department of Pathology, Peking University Cancer Hospital & Institute Beijing, China
| | - Qingfeng Zheng
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery, Peking University Cancer Hospital & Institute Beijing, China
| | - Shi Yan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery, Peking University Cancer Hospital & Institute Beijing, China
| | - Yuanyuan Ma
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery, Peking University Cancer Hospital & Institute Beijing, China
| | - Jianzhi Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery, Peking University Cancer Hospital & Institute Beijing, China
| | - Jian Fang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Respiratory Medicine, Peking University Cancer Hospital & Institute Beijing, China
| | - Nan Wu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery, Peking University Cancer Hospital & Institute Beijing, China
| | - Huijuan Wu
- Beijing Center for Physical and Chemical Analysis Beijing, China
| | - Yue Yang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery, Peking University Cancer Hospital & Institute Beijing, China
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15
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Bodenstine TM, Seftor REB, Khalkhali-Ellis Z, Seftor EA, Pemberton PA, Hendrix MJC. Maspin: molecular mechanisms and therapeutic implications. Cancer Metastasis Rev 2013; 31:529-51. [PMID: 22752408 DOI: 10.1007/s10555-012-9361-0] [Citation(s) in RCA: 81] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Maspin, a non-inhibitory member of the serine protease inhibitor superfamily, has been characterized as a tumor suppressor gene in multiple cancer types. Among the established anti-tumor effects of Maspin are the inhibition of cancer cell invasion, attachment to extracellular matrices, increased sensitivity to apoptosis, and inhibition of angiogenesis. However, while significant experimental data support the role of Maspin as a tumor suppressor, clinical data regarding the prognostic implications of Maspin expression have led to conflicting results. This highlights the need for a better understanding of the context dependencies of Maspin in normal biology and how these are perturbed in the context of cancer. In this review, we outline the regulation and roles of Maspin in normal and developmental biology while discussing novel evidence and emerging theories related to its functions in cancer. We provide insight into the immense therapeutic potential of Maspin and the challenges related to its successful clinical translation.
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Affiliation(s)
- Thomas M Bodenstine
- Children's Hospital of Chicago Research Center, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, 225 E. Chicago Avenue, Box 222, Chicago, IL 60611, USA
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16
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Berardi R, Morgese F, Onofri A, Mazzanti P, Pistelli M, Ballatore Z, Savini A, De Lisa M, Caramanti M, Rinaldi S, Pagliaretta S, Santoni M, Pierantoni C, Cascinu S. Role of maspin in cancer. Clin Transl Med 2013; 2:8. [PMID: 23497644 PMCID: PMC3602294 DOI: 10.1186/2001-1326-2-8] [Citation(s) in RCA: 88] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2012] [Accepted: 01/28/2013] [Indexed: 02/08/2023] Open
Abstract
Maspin (mammary serine protease inhibitor), is a member of the serine protease inhibitor/non-inhibitor superfamily. Its expression is down-regulated in breast, prostate, gastric and melanoma cancers but over-expressed in pancreatic, gallbladder, colorectal, and thyroid cancers suggesting that maspin may play different activities in different cell types. However, maspin expression seems to be correlated with better prognosis in prostate, bladder, lung, gastric, colorectal, head and neck, thyroid and melanoma cancer. In breast and ovarian cancer maspin significance is associated with its subcellular localization: nucleus maspin expression correlates with a good prognosis, whilst in pancreatic cancer it predicts a poor prognosis. Since tumor metastasis requires the detachment and invasion of tumor cells through the basement membrane and stroma, a selectively increased adhesion by the presence of maspin may contribute to the inhibition of tumor metastasis. Furthermore the different position of maspin inside the cell or its epigenetic modifications may explain the different behavior of the expression of maspin between tumors. The expression of maspin might be useful as a prognostic and possibly predictive factor for patients with particular types of cancer and data can guide physicians in selecting therapy. Its expression in circulating tumor cells especially in breast cancer, could be also useful in clinical practice along with other factors, such as age, comorbidities, blood examinations in order to select the best therapy to be carried out. Focusing on the malignancies in which maspin showed a positive prognostic value, therapeutic approaches studied so far aimed to re-activate a dormant tumor suppressor gene by designed transcription factors, to hit the system that inhibits the expression of maspin, to identify natural substances that can determine the activation and the expression of maspin or possible "molecules binds" to introduce maspin in cancer cell and gene therapy capable of up-regulating the maspin in an attempt to reduce primarily the risk of metastasis.Further studies in these directions are necessary to better define the therapeutic implication of maspin.
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Affiliation(s)
- Rossana Berardi
- Medical Oncology Unit, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi di Ancona, Via Conca, Ancona, 71-60126, Italy
| | - Francesca Morgese
- Medical Oncology Unit, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi di Ancona, Via Conca, Ancona, 71-60126, Italy
| | - Azzurra Onofri
- Medical Oncology Unit, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi di Ancona, Via Conca, Ancona, 71-60126, Italy
| | - Paola Mazzanti
- Medical Oncology Unit, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi di Ancona, Via Conca, Ancona, 71-60126, Italy
| | - Mirco Pistelli
- Medical Oncology Unit, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi di Ancona, Via Conca, Ancona, 71-60126, Italy
| | - Zelmira Ballatore
- Medical Oncology Unit, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi di Ancona, Via Conca, Ancona, 71-60126, Italy
| | - Agnese Savini
- Medical Oncology Unit, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi di Ancona, Via Conca, Ancona, 71-60126, Italy
| | - Mariagrazia De Lisa
- Medical Oncology Unit, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi di Ancona, Via Conca, Ancona, 71-60126, Italy
| | - Miriam Caramanti
- Medical Oncology Unit, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi di Ancona, Via Conca, Ancona, 71-60126, Italy
| | - Silvia Rinaldi
- Medical Oncology Unit, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi di Ancona, Via Conca, Ancona, 71-60126, Italy
| | - Silvia Pagliaretta
- Medical Oncology Unit, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi di Ancona, Via Conca, Ancona, 71-60126, Italy
| | - Matteo Santoni
- Medical Oncology Unit, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi di Ancona, Via Conca, Ancona, 71-60126, Italy
| | - Chiara Pierantoni
- Medical Oncology Unit, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi di Ancona, Via Conca, Ancona, 71-60126, Italy
| | - Stefano Cascinu
- Medical Oncology Unit, Università Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti Umberto I, GM Lancisi, G Salesi di Ancona, Via Conca, Ancona, 71-60126, Italy
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Vered M, Allon I, Tunis TS, Buchner A, Dayan D. Expression of the homeostasis-related markers, maspin, heat shock proteins 70 & 90, glutathione S-transferase, aquaporin 5 and NF-kB in young and old labial and palatal salivary glands. Exp Gerontol 2013; 48:444-50. [PMID: 23416193 DOI: 10.1016/j.exger.2013.02.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2012] [Revised: 02/05/2013] [Accepted: 02/07/2013] [Indexed: 12/25/2022]
Abstract
Intraoral salivary glands undergo remarkable age-related morphologic changes. This study investigated the expression of a panel of molecular markers known for cellular homeostatic activity, dependent on age and location of the salivary glands. Samples taken from healthy subjects were classified according to age ("young" <45 years, n=51, and "old" ≥60 years, n=45) and location (lip, n=47 and palate, n=49). They were immunohistochemically stained for mammary serine protease inhibitor (maspin), heat shock protein (HSP)70, HSP90, glutathione S-transferase (GST), aquaporine5 (AQP5), and nuclear factor kappa-B (NF-κB) for assessment of their expression in acini and ducts, and in cytoplasmic and nuclear compartments. Results were expressed as the mean percentage of positively stained component per age group, gland location and type of cell and cellular compartment. Statistical analysis was performed by two-way ANOVA and crosstabs. The expression of maspin was lower in the old group in both the palatal and labial glands (acini and ducts, cytoplasm and nuclei) compared to the young group (p<0.05). In both age groups, when compared to labial glands, palatal glands exhibited higher expression of HSP70 (p<0.05) and lower expression of AQP5 (p<0.001) and NF-κB (p=0.018). Collectively, the low expression of factors capable of preserving cellular homeostasis (i.e., maspin and AQP5) vis-à-vis a high expression of factors that are also related to cell survival (i.e., HSPs) that was demonstrated in the old palatal glands may point to their high vulnerability to undergo selective phenotypic changes.
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Affiliation(s)
- Marilena Vered
- Department of Oral Pathology and Oral Medicine, School of Dental Medicine, Tel Aviv University, Tel Aviv, Israel.
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18
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Abd El Atti RM. The significance of immunohistochemical expression of maspin in basal-like breast cancer. EGYPTIAN JOURNAL OF PATHOLOGY 2012; 32:204-210. [DOI: 10.1097/01.xej.0000421478.65830.6e] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
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Abdou AG, Maraee AH, El-Monaem Shoeib MA, Abo Saida AM. Maspin expression in epithelial skin tumours: an immunohistochemical study. J Cutan Aesthet Surg 2011; 4:111-7. [PMID: 21976902 PMCID: PMC3183715 DOI: 10.4103/0974-2077.85028] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
BACKGROUND Maspin is a member of the serpin family of protease inhibitors and is thought to inhibit carcinoma invasion, metastasis, angiogenesis and induce apoptosis. AIM The aim of this work is to investigate maspin expression in cutaneous basal and squamous cell carcinomas by means of immunohistochemistry. MATERIALS AND METHODS This study was carried out on 43 patients, 25 basal cell carcinoma (BCC) and 18 squamous cell carcinoma (SCC) together with ten apparently healthy volunteers as a control group. RESULTS There was a significant difference between the malignant and control groups regarding maspin expression since all control cases showed maspin expression compared to 60.5% (26/43) positivity in malignant cases. Maspin positive expression tended to be of higher percentage in SCC (77.8%) compared to BCC (48%) (P = 0.06) and the strong intensity of maspin was also significantly in favour of SCC compared to BCC (P = 0.02). The staining of both the cytoplasm and nuclei was seen in 27.7% of SCC and 12% of BCC and was significantly in favour of older age group (P = 0.02) and the adenoid variant (P = 0.04) of the latter. CONCLUSIONS Maspin is associated with terminal squamous differentiation. Nuclear staining of maspin is seen in both BCC and SCC with a suggested tumour suppressor role in BCC.
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Affiliation(s)
- Asmaa Gaber Abdou
- Department of Pathology, Faculty of Medicine, Menofiya University, Shebein Elkom, Egypt
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Goulet B, Chan G, Chambers AF, Lewis JD. An emerging role for the nuclear localization of maspin in the suppression of tumor progression and metastasis. Biochem Cell Biol 2011; 90:22-38. [PMID: 22047058 DOI: 10.1139/o11-053] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Maspin, a member of the serpin family of serine protease inhibitors, was originally identified as a tumor suppressor that is expressed in normal mammary epithelial cells but is reduced or absent in breast carcinomas. Early enthusiasm for maspin as a biomarker for disease progression has been tempered by clinical data that associates maspin with favourable outcomes in some studies and poor prognosis in others. Here, we review all of the published clinical studies for maspin in breast and ovarian cancers and propose that the apparent discordance between clinical reports is a consequence of differential cellular distribution of maspin. Indeed, it was thought that an extracellular pool of maspin possessed tumor suppressor activity, acting by inhibiting migration and increasing cell adhesion. Recent evidence from our group and others indicates, however, that the nuclear localization of maspin in cancer cells is necessary for its tumor suppressor activity. We provide additional data here to demonstrate that nuclear-localized maspin binds to chromatin and is required to effectively prevent cells from metastasizing. Our knowledge of other serpins that localize to the nucleus should help to inform future studies of nuclear maspin. Elucidation of the molecular mechanisms regulating the localization and activities of maspin should pave the way for the development of improved diagnostics and therapies for cancer.
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Affiliation(s)
- Brigitte Goulet
- London Regional Cancer Program, Translational Prostate Cancer Research Group, London, ON N6A 4L6, Canada
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Märkl B, Arnholdt HM, Jähnig H, Schenkirsch G, Herrmann RA, Haude K, Spatz H, Anthuber M, Schlimok G, Oruzio D. Shift from cytoplasmic to nuclear maspin expression correlates with shorter overall survival in node-negative colorectal cancer. Hum Pathol 2010; 41:1024-33. [PMID: 20334895 DOI: 10.1016/j.humpath.2009.10.021] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2009] [Revised: 09/24/2009] [Accepted: 10/06/2009] [Indexed: 12/22/2022]
Abstract
Maspin has been characterized as a potent tumor suppressor in many in vitro and in vivo studies. In contrast, in stage III colon cancer, an association with shorter overall survival as well as sensitivity to chemotherapy was found for cases with nuclear maspin expression. Because 20% of node-negative colorectal cancer cases show a fatal clinical course, we hypothesized that immunohistochemical maspin expression could be of help to identify higher-risk cases. Therefore, we analyzed survival in a study employing 156 cases of stage I/II colorectal cases. Immunohistochemical cytoplasmic and/or nuclear maspin expression was found in 72% and 48% of the cases, respectively. Significant correlations between cytoplasmic expression and high tumor grade (P < .01) and between nuclear expression and tumor budding (P < .001) were shown. No differences concerning overall survival and immunohistochemical maspin expression were found when the complete collective was analyzed. However, evaluation of the pT3 cases revealed a highly significant worse mean overall survival of cases with a combination of nuclear expression and cytoplasmic loss of maspin compared to cases with the opposite expression pattern nuclear loss and cytoplasmic expression (mean overall survival 40 versus 63 months, respectively; P < .001). The other possible combinations (complete positive and complete negative) showed intermediate mean overall survival times with 54 and 49 months, respectively. Our findings suggest a compartment-dependent function of maspin in colorectal cancer, which can be useful in identifying stage II cases with a higher risk for fatal outcome with a possible benefit from adjuvant chemotherapy.
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Affiliation(s)
- Bruno Märkl
- Institute of Pathology, Klinikum Augsburg, Augsburg 86156, Germany.
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Joensuu KM, Leidenius MHK, Andersson LC, Heikkilä PS. High expression of maspin is associated with early tumor relapse in breast cancer. Hum Pathol 2009; 40:1143-51. [PMID: 19427667 DOI: 10.1016/j.humpath.2009.02.006] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2008] [Revised: 02/16/2009] [Accepted: 02/19/2009] [Indexed: 11/25/2022]
Abstract
Maspin is a serine protease inhibitor with tumor suppressor activity. Maspin can suppress tumor growth and metastasis in vivo and tumor cell motility and invasion in vitro. Maspin also modulates apoptosis of tumor cells, possibly by modulating the expression of the B-cell lymphoma-2 family member. p53 regulates the expression of the tumor suppressor gene maspin. Breast cancer is known for its propensity to recur even after decades. The biology behind this phenomenon of tumor dormancy is poorly understood. This study was conducted to clarify the role of maspin and B-cell lymphoma-2 in early and late recurring breast cancer. The expression of maspin, B-cell lymphoma-2, p53, and estrogen receptor was studied by immunohistochemistry in 73 primary breast cancers and in their metastatic relapses detected within 2 years, or 5 or 10 years after primary surgery. The cytoplasmic expression of maspin was significantly higher in the primary tumors of the early metastasizing breast cancers (first tumor relapse within 2 years) and also in their metastases compared to late metastasizing cancers. An opposite activity was observed in the expression of B-cell lymphoma-2. The level of B-cell lymphoma-2 staining was lower in the early relapsing cancers and significantly lower in their metastases, compared to tumors which metastasized 5 or 10 years after primary surgery. High cytoplasmic expression of maspin and low expression of B-cell lymphoma-2 in primary breast cancer predict early tumor relapse.
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Affiliation(s)
- Kristiina M Joensuu
- Department of Pathology and HUSLAB, Helsinki University Central Hospital, Helsinki, Finland.
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