• Casein nanoparticles
• Colon cancer
• MMP-7
• Pickering emulsion
• Targeted delivery

• Caseins/chemistry
• Emulsions/chemistry
• Humans
• Nanoparticles/chemistry
• Drug Carriers/chemistry
• Drug Delivery Systems
• Cell Line, Tumor
• Matrix Metalloproteinase 7/metabolism
• Drug Liberation
• Acrylic Resins/chemistry

• MMP7
• Matrilysin
• Monomeric
• Purification
• Refolding

• Matrix Metalloproteinase 7/genetics
• Escherichia coli/genetics
• Escherichia coli/metabolism

• Adenocarcinoma
• Matrix metalloproteinase-7
• Prognosis
• Spread through air spaces

• Cell culture
• Cornea
• Corneal endothelium
• Fuchs endothelial corneal dystrophy
• Matrix metalloproteinases
• Tissue inhibitor of matrix metalloproteinases

• SW480
• adhesion
• gelatinase
• invasion
• lipopolysaccharide
• purple rice

• Crohn’s disease
• matrix metalloproteinases
• membrane-bound and soluble PD-L1
• myo-/fibroblasts

Many studies have investigated the association between matrix metalloproteinase polymorphisms and lung cancer susceptibility. However, the results are still controversial. To clarify these associations, we conducted a meta-analysis.

A systematic search of studies was conducted in PubMed, Embase, and China National Knowledge Infrastructure. Overall and subgroup analysis stratified by ethnicity was conducted. OR with 95% CI was used to assess the strength of the association. Furthermore, false-positive report probability (FPRP) tests were also performed for associations obtained in this meta-analysis.

Twenty-four studies, including 10,099 cases and 9,395 controls, were analyzed. Nine polymorphisms were reported. For MMP1 -1607 1G/2G and MMP7 -181 A/G, increased lung cancer risk was found in Asians. For MMP2 -1306 C/T and MMP2 -735 C/T, decreased lung cancer risk was found in both “diverse populations” and Asians. For MMP9 -1562, C/T decreased lung cancer risk was found in both “diverse populations” and Caucasians. For MMP13 -77A/G, the A/G genotype decreased lung cancer risk in Asians. However, only associations between MMP1 -1607 1G/2G, MMP2 -1306 C/T, MMP2 -735 C/T, and MMP7 -181 A/G and lung cancer risk were considered noteworthy according to FPRP tests. There was no association between MMP3 -1171 5A/6A, MMP9 R279Q, and MMP12 -82A/G and lung cancer risk.

Our meta-analysis suggested that MMP1 -1607 1G/2G and MMP7 -181 A/G were risk factors for lung cancer, while MMP2 -1306 C/T, MMP2 -735 C/T, MMP9 -1562 C/T, and MMP13 -77A/G might be protective factors. However, results for MMP9 -1562 C/T and MMP13 -77A/G should be interpreted with caution due to the probability of false-positive reports.

• Matrix metalloproteinases
• lung cancer
• meta-analysis
• polymorphisms

We sought to apply Shannon’s entropy to determine colorectal cancer genes in a microarray dataset.

In the retrospective study, 36 samples were analysed, 18 colorectal carcinoma and 18 paired normal tissue samples. After identification of the gene fold-changes, we used the entropy theory to identify an effective gene set. These genes were subsequently categorised into homogenous clusters.

We assessed 36 tissue samples. The entropy theory was used to select a set of 29 genes from 3128 genes that had fold-changes greater than one, which provided the most information on colorectal cancer. This study shows that all genes fall into a cluster, except for the R08183 gene.

This study has identified several genes associated with colon cancer using the entropy method, which were not detected by custom methods. Therefore, we suggest that the entropy theory should be used to identify genes associated with cancers in a microarray dataset.

• Cancer
• Colorectal
• Microarray
• Statistical Model

The strong invasive and metastatic nature of non-small cell lung cancer (NSCLC) leads to poor prognosis. Collagen triple helix repeat containing 1 (CTHRC1) is involved in cell migration, motility and invasion. The object of this study is to investigate the involvement of CTHRC1 in NSCLC invasion and metastasis.

A proteomic analysis was performed to identify the different expression proteins between NSCLC and normal tissues. Cell lines stably express CTHRC1, MMP7, MMP9 were established. Invasion and migration were determined by scratch and transwell assays respectively. Clinical correlations of CTHRC1 in a cohort of 230 NSCLC patients were analysed.

CTHRC1 is overexpressed in NSCLC as measured by proteomic analysis. Additionally, CTHRC1 increases tumour cell migration and invasion in vitro. Furthermore, CTHRC1 expression is significantly correlated with matrix metalloproteinase (MMP)7 and MMP9 expression in sera and tumour tissues from NSCLC. The invasion ability mediated by CTHRC1 were mainly MMP7- and MMP9-dependent. MMP7 or MMP9 depletion significantly eradicated the pro-invasive effects mediated by CTHRC1 on NSCLC cells. Clinically, patients with high CTHRC1 expression had poor survival.

CTHRC1 serves as a pro-metastatic gene that contributes to NSCLC invasion and metastasis, which are mediated by upregulated MMP7 and MMP9 expression. Targeting CTHRC1 may be beneficial for inhibiting NSCLC metastasis.

The online version of this article (10.1186/s12885-018-4317-6) contains supplementary material, which is available to authorized users.

• CTHRC1
• Invasion/metastasis
• Lung cancer
• MMP7
• MMP9

• acute myeloid leukemia
• matrix metalloproteinase-7
• phosphatase and tension homolog

• cell adhesion
• cell-surface protein
• matrix metalloproteinase (MMP)
• shedding
• tumor metastasis

• Compartmentalization
• Membrane recognition
• Membrane trafficking
• Peripheral membrane protein
• Protease
• Sheddase

• biosensors
• metalloproteinases
• nanopillars
• nanotags
• stroke
• surface-enhanced Raman spectroscopy
• vascular diseases

• Animals
• Biomarkers/blood
• Biomarkers/metabolism
• Carbon Monoxide/chemistry
• Ligands
• Male
• Matrix Metalloproteinases/blood
• Matrix Metalloproteinases/metabolism
• Nanoparticles/chemistry
• Optical Phenomena
• Organometallic Compounds/chemistry
• Particle Size
• Rats
• Rats, Wistar
• Surface Properties
• Vascular Diseases/blood
• Vascular Diseases/diagnostic imaging
• Vascular Diseases/metabolism

• Gold nanoparticles
• contrast media
• multiphoton microscopy
• optical sensing
• peptide

• Amino Acid Sequence
• Cations, Divalent/analysis
• Contrast Media/chemistry
• Dimerization
• Gold/chemistry
• Humans
• Luminescence
• Matrix Metalloproteinase 7/analysis
• Metal Nanoparticles/chemistry
• Metal Nanoparticles/ultrastructure
• Microscopy, Confocal/methods
• Peptides/chemistry
• Photons
• Zinc/analysis

Oligodendrogliomas are infiltrative astrocytic tumors. They constitute about 1-5% of intracranial tumors. These have been graded into benign and malignant grades. The single nucleotide polymorphisms (SNPs) in the promoter regions of MMP genes may influence tumor development and progression. This study was done to explore the correlations of the promoter SNPs in MMP-1, MMP-2 and MMP-7 genes susceptibility in development and progression of oligodendrogliomas.

We aimed to investigate the association of MMP1 (−1607A > G), MMP-2 (−1306 C/T) and MMP-7(−181A > G) gene polymorphism in oligodendrogliomas (grade I, II, III).

In the present case control study, we enrolled a total of 30 cases of oligodendrogliomas (grade I to III) confirmed by histopathology and 30 healthy cases as control. Polymorphism for MMP-1 gene (−1607A > G), MMP-2 (−1306 C/T), MMP-7(−181A > G) were genotyped by restriction fragment length polymorphism.

Frequencies of MMP-1 (−1607A > G) genotypes and 2G alleles were significantly associated with the cases of oligodendrogliomas (30%) in relation to healthy controls (13%). [OR = 6.89; P = 0.02; 95%CI= (1.33-35.62)] and [OR = 2.66; P =0.01; 95% CI= (1.26-5.64)]. A significant association of MMP-2 (−1306C/T) polymorphism with oligodendroglioma (P = 0.54) was not found, suggesting that MMP-2 (−1306C/T) polymorphism is not associated with increased oligodendroglioma susceptibility. Frequencies of MMP-7(−181A > G) genotypes and 2G alleles were significantly associated with the cases of oligodendrogliomas (33.33%) in relation to healthy controls (13.33%). [OR = 5.65; P = 0.02; 95%CI= (1.26-25.36)] and [OR = 2.49; P =0.01; 95% CI= (1.17-5.27)].

MMP-1 (−1607 A > G), MMP-7(−181A > G) genotypes and 2G alleles were significantly associated with oligodendroglioma (grade I, II, III), but MMP-2 (−1306C/T) polymorphism is not associated with increased oligodendroglioma susceptibility.

• Oligodendrogliomas
• polymerase chain reaction
• polymorphism

Because earlier studies showed the cell surface heparan sulfate proteoglycan, syndecan-2, sheds from colon cancer cells in culture, the functional roles of shed syndecan-2 were assessed. A non-cleavable mutant of syndecan-2 in which the Asn¹⁴⁸-Leu¹⁴⁹ residues were replaced with Asn¹⁴⁸-Ile¹⁴⁹, had decreased shedding, less cancer-associated activities of syndecan-2 in vitro, and less syndecan-2-mediated metastasis of mouse melanoma cells in vivo, suggesting the importance of shedding on syndecan-2-mediated pro-tumorigenic functions. Indeed, shed syndecan-2 from cancer-conditioned media and recombinant shed syndecan-2 enhanced cancer-associated activities, and depletion of shed syndecan-2 abolished these effects. Similarly, shed syndecan-2 was detected from sera of patients from advanced carcinoma (625.9 ng/ml) and promoted cancer-associated activities. Furthermore, a series of syndecan-2 deletion mutants showed that the tumorigenic activity of shed syndecan-2 resided in the C-terminus of the extracellular domain and a shed syndecan-2 synthetic peptide (16 residues) was sufficient to establish subcutaneous primary growth of HT29 colon cancer cells, pulmonary metastases (B16F10 cells), and primary intrasplenic tumor growth and liver metastases (4T1 cells). Taken together, these results demonstrate that shed syndecan-2 directly enhances colon cancer progression and may be a promising therapeutic target for controlling colon cancer development.

• Allosteric Regulation
• Amino Acid Sequence
• Cell Line, Tumor
• Cell Membrane/metabolism
• Cholesterol/chemistry
• Cholesterol/metabolism
• Humans
• Lipid Bilayers/chemistry
• Lipid Bilayers/metabolism
• Matrix Metalloproteinase 7/chemistry
• Matrix Metalloproteinase 7/metabolism
• Molecular Sequence Data
• Protein Binding
• Protein Transport
• Static Electricity
• Transport Vesicles/metabolism

• R01 GM057289 NIGMS NIH HHS
• S10 RR022341 NCRR NIH HHS
• R01 GM57289 NIGMS NIH HHS

Regenerating islet-derived family, member 4 (Reg IV), a member of the Reg gene family, has been reported to be overexpressed in gastrointestinal tract cancers. Reg IV overexpression in tumor cells has been associated with carcinogenesis, tissue regeneration, proliferation and resistance to apoptosis. Reg IV activates the epidermal growth factor receptor (EGFR) signaling pathway in colon cancer and increases expression of B-cell lymphoma-2 (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl), which are associated with the inhibition of apoptosis, results in mitogenic signaling in colon cancer cells, increase cell proliferation, metastasis and decreased apoptosis. Reg IV treatment inhibits 5-fluorouracil induced apoptosis, at least two mechanisms are involved in inhibition of apoptosis by Reg IV, including Bcl-2 and dihydropyrimidine dehydrogenase (DPD). These studies may lead to novel therapeutic strategies for cancers expressing Reg IV. Recently, one proteoglycan was confirmed to disrupt this signaling pathway to perform antitumor effect. This review summaries current knowledge of the expression and roles of Reg IV in human colorectal cancer, describes the possible signaling pathway which Reg IV activates, and discusses the relevance of Reg IV as a potential therapeutic target for cancer treatment.

• Cdx2
• EGFR/Akt/AP-1 pathway
• Reg IV
• colorectal cancer
• targeted therapy

Although matrix metalloproteinase (MMP)-7 expression is correlated with increased metastatic potential in human colon cancer cells, the underlying molecular mechanism of invasive phenotype remains unknown. In the current study, we investigated the regulatory effects of membrane NADPH oxidase (NOX) and AMP activated protein kinase (AMPK) on MMP-7 expression and invasive phenotype change in colon cancer cells.

Production of superoxide anion was measured by lucigenin chemiluminescence assay using whole cells and protein extracts (NADPH oxidase activity), and intracellular reactive oxygen species (ROS) by fluorescence microscopy using 2’,7’-dichlorofluorescein diacetate (DCF-DA). Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were used to measure mRNA and protein levels, respectively. siRNA transfection was used to assess involvement of genes in cancer invasion, which were identified by Matrigel transwell invasion assay. Luciferase reporter assay was performed to identify transcription factors linked to gene expression.

Under basal conditions, less invasive human colon cancer cells (HT29 and Caco-2) showed low MMP-7 expression but high NOX1 expression and AMPK phosphorylation. Treatment of HT29 and Caco-2 cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) induced an invasive phenotype response along with corresponding increases in ROS production and NOX2 and MMP-7 expression as well as reduced AMPK phosphorylation, which resemble basal conditions of highly invasive human colon cancer cells (SW620 and HCT116). In addition, inverse regulation between AMPK phosphorylation and NOX2 and MMP-7 expression was observed in HT29 cells treated with different concentrations of exogenous hydrogen peroxide. TPA-induced invasive phenotype in HT29 cells was abolished by treatment with Vit. E, DPI, apocynin, and NOX2 siRNA but not NOX1 siRNA, indicating NOX2-derived ROS production induced an invasive phenotype. TPA-induced induction of MMP-7 expression was suppressed by AP-1, NF-κB, and MAPK (ERK, p38, and JNK) inhibitors, whereas TPA-induced expression of NOX2 and its regulators, p47phox and p67phox, was blocked by p38 and NF-κB inhibitors.

Molecular switch from NOX1 to NOX2 in colon cancer cells induces ROS production and subsequently enhances MMP-7 expression by deactivating AMPK, which otherwise inhibits stimulus-induced autoregulation of ROS and NOX2 gene expression.

The online version of this article (doi:10.1186/s12943-015-0379-0) contains supplementary material, which is available to authorized users.

• acidic lipid
• extracellular matrix
• metalloproteinase, pericellular proteolysis
• substrate preference

• Binding, Competitive
• Cardiolipins/chemistry
• Cardiolipins/metabolism
• Cell Adhesion Molecules/chemistry
• Cell Line, Tumor
• Cell Membrane/enzymology
• Cholesterol Esters/chemistry
• Cholesterol Esters/metabolism
• Dipeptides/chemistry
• Dipeptides/pharmacology
• Fibronectins/chemistry
• Humans
• Hydroxamic Acids/chemistry
• Hydroxamic Acids/pharmacology
• Kinetics
• Matrix Metalloproteinase 7/chemistry
• Matrix Metalloproteinase 7/metabolism
• Matrix Metalloproteinase Inhibitors/chemistry
• Matrix Metalloproteinase Inhibitors/pharmacology
• Protein Binding
• Proteolysis
• Sulfoglycosphingolipids/chemistry
• Sulfoglycosphingolipids/metabolism
• Kalinin

• Colorectal cancer
• IGFBP-2
• Oxidation
• Protein complexes
• Sialylation
• α2 macroglobulin

• Amino Acid Sequence
• Colorimetry
• Cysteine/chemistry
• Gold/chemistry
• Humans
• Hydrogen-Ion Concentration
• Immobilized Proteins/chemistry
• Immobilized Proteins/metabolism
• Matrix Metalloproteinase 7/analysis
• Metal Nanoparticles/chemistry
• Molecular Sequence Data
• Peptides/chemistry
• Peptides/metabolism
• Saliva/enzymology
• Salivary Gland Neoplasms/enzymology
• Salivary Gland Neoplasms/pathology

Abnormal regulation of Wnt/β-catenin signaling and subsequently increased β-catenin expression have been found to be involved in the proliferation and growth of colon cancer cells. Whether the down-regulation of β-catenin in colon cancer may result in compromised invasion and migration in vitro still remains to be determined.

A human colon cancer cell line (LoVo cells) was transfected with small interfering RNA (siRNA) targeting β-catenin. RT-PCR, Western blot assay, flow cytometry, cell adhesion assay, scratch wound assay, and matrigel invasion assay were performed, and the correlation between cell invasion and migration and β-catenin expressions was analyzed.

siRNA-mediated down-regulation of β-catenin elevated the E-cadherin expression but reduced the MMP-7 and CD44v6 expressions, which increased the adhesion between LoVo cells but decreased the adhesion of LoVo cells to fibronectin. Significant inhibition of cell invasion and migration was also observed following RNA interference with β-catenin siRNA.

siRNA-mediated downregulation of β-catenin could be valuable for defining gene expression and functional programs downstream of oncogenic β-catenin signals, which, in turn, may be helpful to isolate novel diagnostic markers, and for designing tumor-specific intervention at downstream targets of oncogenic β-catenin.

The regenerating islet-derived members (Reg), a group of small secretory proteins, which are involved in cell proliferation or differentiation in digestive organs, are upregulated in several gastrointestinal cancers, functioning as trophic or antiapoptotic factors. Regenerating islet-derived type IV (RegIV), a member of the Reg gene family, has been reported to be overexpressed in gastroenterological cancers. RegIV overexpression in tumor cells has been associated with carcinogenesis, cell growth, survival and resistance to apoptosis. Cancer tissue expressing RegIV is generally associated with more malignant characteristics than that without such expression, and RegIV is considered a novel prognostic factor as well as diagnostic marker in some gastroenterological cancers. We previously investigated the expression levels of RegIV mRNA of 202 surgical colorectal cancer specimens with quantitative real-time reverse-transcriptase polymerase chain reaction and reported that a higher level of RegIV gene expression was a significant independent predictor of colorectal cancer. The biologic functions of RegIV protein in cancer tissue, associated with carcinogenesis, anti-apoptosis and invasiveness, are being elucidated by molecular investigations using transfection techniques or neutralizing antibodies of RegIV, and the feasibility of antibody therapy targeting RegIV is being assessed. These studies may lead to novel therapeutic strategies for gastroenterological cancers expressing RegIV. This review article summarizes the current information related to biological functions as well as clinical importance of RegIV gene to clarify the significance of RegIV expression in gastroenterological cancers.

• Regenerating islet-derived type IV protein
• Gastrointestinal neoplasms
• Prognosis
• Epidermal growth factor receptor/protein kinase B

• Autofluorescence endoscopy
• Confocal endomicroscopy
• Endoscopy
• Molecular imaging
• Molecular probes, Near-infrared fluorescence imaging
• Targeted endoscopic imaging

• cholangiocarcinoma
• matrix metalloprotease
• matrix metalloprotease-7
• prognostic factor

Heterogeneity among cells that constitute a solid tumor is important in determining disease progression. Our previous work established that, within a population of metastatic colonic tumor cells, there are minor subpopulations of cells with stable differences in their intrinsic mitochondrial membrane potential (ΔΨm), and that these differences in ΔΨm are linked to tumorigenic phenotype. Here we expanded this work to investigate primary mammary, as well as colonic, tumor cell lines. We show that within a primary mammary tumor cell population, and in both primary and metastatic colonic tumor cell populations, there are subpopulations of cells with significant stable variations in intrinsic ΔΨm. In each of these 3 tumor cell populations, cells with relatively higher intrinsic ΔΨm exhibit phenotypic properties consistent with promotion of tumor cell survival and expansion. However, additional properties associated with invasive potential appear in cells with higher intrinsic ΔΨm only from the metastatic colonic tumor cell line. Thus, it is likely that differences in the intrinsic ΔΨm among cells that constitute primary mammary tumor populations, as well as primary and metastatic colonic tumor populations, are markers of an acquired tumor phenotype which, within the context of the tumor, influence the probability that particular cells will contribute to disease progression.

• cell adhesion
• enzyme mechanisms
• extracellular matrix proteins
• fibronectin
• laminin
• matrix metalloproteinase
• tumor metastases
• cholesterol sulfate
• mmp-7
• matrilysin

• Cell Adhesion Molecules/metabolism
• Cell Line, Tumor
• Cell Movement/drug effects
• Cholesterol Esters/pharmacology
• Dose-Response Relationship, Drug
• Fibronectins/metabolism
• Humans
• Matrix Metalloproteinase 7/metabolism
• Neoplasm Metastasis
• Neoplasms/metabolism
• Neoplasms/pathology
• Serine Proteinase Inhibitors/pharmacology
• Substrate Specificity/drug effects
• Kalinin

• Cell Movement/genetics
• Cells/metabolism
• Colonic Neoplasms/genetics
• Colonic Neoplasms/metabolism
• Endothelial Cells/metabolism
• Extracellular Matrix/genetics
• Extracellular Matrix/metabolism
• Humans
• Integrins/genetics
• Integrins/metabolism
• Matrix Metalloproteinase 2/genetics
• Matrix Metalloproteinase 2/metabolism
• Matrix Metalloproteinase 9/genetics
• Matrix Metalloproteinase 9/metabolism
• Matrix Metalloproteinases/genetics
• Matrix Metalloproteinases/metabolism
• Matrix Metalloproteinases/physiology
• Neoplasms/genetics
• Neoplasms/metabolism
• RNA, Small Interfering/genetics
• RNA, Small Interfering/metabolism
• Signal Transduction/genetics
• Thymosin/genetics
• Thymosin/metabolism
• Vascular Endothelial Growth Factor A/genetics
• Vascular Endothelial Growth Factor A/metabolism

• Adult
• Aged
• Biomarkers, Tumor/analysis
• Female
• Humans
• Immunohistochemistry
• Male
• Matrix Metalloproteinase 7/analysis
• Matrix Metalloproteinase 7/blood
• Matrix Metalloproteinase 7/genetics
• Middle Aged
• Multivariate Analysis
• Neoplasm Metastasis
• Urinary Bladder Neoplasms/mortality
• Urinary Bladder Neoplasms/pathology