Spectrum of matrix metalloproteinase expression in primary and metastatic colon cancer: relationship to the tissue inhibitors of metalloproteinases and membrane type-1-matrix metalloproteinase

Collins, Hilary M.; Morris, Teresa; Watson, Susan A.

doi:10.1054/bjoc.2001.1831

Cited by 54 publications

(44 citation statements)

References 23 publications

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“…The observed increase in MMP-2 expression observed in tumor samples is consistent with previous studies of breast (41,42), colon (43)(44)(45)(46)(47), stomach (48,49), lung (50 -53), rectal (43,54), and kidney cancer (55)(56)(57). Whereas a strong association of increased MMP-3 has been found in breast cancer (41, 58 -61), the increased expression levels observed in other tumor types are not as well supported by published literature.…”

Section: Sibling Expression and Tumor Progressionsupporting

confidence: 91%

Small Integrin Binding Ligand N -Linked Glycoprotein Gene Family Expression in Different Cancers

Fisher

Jain

Tayback

et al. 2004

Clinical Cancer Research

109

115

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Purpose: Members of the small integrin binding ligand N-linked glycoprotein (SIBLING) gene family have the capacity to bind and modulate the activity of matrix metalloproteinases (MMPs). The expression levels of five SIBLING gene family members [bone sialoprotein (BSP), osteopontin (OPN), dentin matrix protein 1 (DMP1), matrix extracellular phosphoglycoprotein (MEPE), and dentin sialophosphoprotein (DSPP)] and certain MMPs were determined using a commercial cancer array.Experimental Design: Cancer profiling arrays containing normalized cDNA from both tumor and corresponding normal tissues from 241 individual patients were used to screen for SIBLING and MMP expression in nine distinct cancer types.Results: Significantly elevated expression levels were observed for BSP in cancer of the breast, colon, stomach, rectum, thyroid, and kidney; OPN in cancer of the breast, uterus, colon, ovary, lung, rectum, and thyroid; DMP1 in cancer of the breast, uterus, colon, and lung; and dentin sialophosphoprotein in breast and lung cancer. The degree of correlation between a SIBLING and its partner MMP was found to be significant within a given cancer type (e.g., BSP and MMP-2 in colon cancer, OPN and MMP-3 in ovarian cancer; DMP1 and MMP-9 in lung cancer). The expression levels of SIBLINGs were distinct within subtypes of cancer (e.g., breast ductal tumors compared with lobular tumors). In general, SIBLING expression increased with cancer stage for breast, colon, lung, and rectal cancer.Conclusions: These results suggest SIBLINGs as potential markers of early disease progression in a number of different cancer types, some of which currently lack vigorous clinical markers.

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Section: Sibling Expression and Tumor Progressionsupporting

confidence: 91%

Small Integrin Binding Ligand N -Linked Glycoprotein Gene Family Expression in Different Cancers

Fisher

Jain

Tayback

et al. 2004

Clinical Cancer Research

109

115

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“…High expression levels of MMP-2 in the malignant epithelium as well as in the surrounding stroma are associated with reduced survival of CRC patients (Collins et al, 2001). In the present study, MMP-2 mRNA was found to be up-regulated (10 times) in colorectal cancer tumor tissues compared to normal tissues (Figure 3).…”

Section: Discussionsupporting

confidence: 54%

Matrix Metalloproteinase-2 (-1306 C>T) Promoter Polymorphism and Risk of Colorectal Cancer in the Saudi Population

Saeed

Alanazi²,

Parine³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic activity against matrix proteins, particularly basement membrane constituents. A single nucleotide polymorphism (SNP) at -1306, which disrupts a Sp1-type promoter site (CCACC box), results in strikingly lower promoter activity with the T allele. In the present study, we investigated whether this MMP-2 genetic polymorphism might be associated with susceptibility to colorectal cancer (CRC) in the Saudi population. We also analyzed MMP-2 gene expression level sin CRC patients and 4 different cancer cell lines. Materials and Methods: TaqMan allele discrimination assays and DNA sequencing techniques were used to investigate the C -1306 T SNP in the MMP-2 gene of Saudi colorectal cancer patients and controls. The MMP-2 gene expression level was also determined in 12 colon cancer tissue samples collected from unrelated patients and histologically normal tissues distant from tumor margins. Results and Conclusions: The MMP-2 C -1306 T SNP in the promoter region was associated with CRC in our Saudi population and the MMP-2 gene expression level was found to be 10 times higher in CRC patients. The MMP-2 C -1306 T SNP is significantly associated with CRC in the Saudi population and this finding suggested that MMP-2 variants might help predict CRC progression risk among Saudis. We propose that analysis of this gene polymorphism could assist in identification of patient subgroups at risk of a poor disease outcome.

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“…Proteins were resolved under denaturing conditions, renatured for 1 hour, and incubated for 18 hours (37jC) in buffer containing 50 mmol/L Tris-HCl (pH 7.5), 150 mmol/L NaCl, and 5 mmol/L CaCl 2 . Gelatinolytic activity was visualized by Coomassie blue staining and quantified by densitometry (15,19). Where indicated, the tissue inhibitor of matrix metalloproteinase 1 (TIMP-1; Chemicon International) was dissolved in PBS and included in incubations.…”

Section: Methodsmentioning

confidence: 99%

“…Indeed, MMP-9 expression has been localized in the tumor stroma, mainly in fibroblasts and inflammatory cells (15,16). Thus, the current paradigm suggests that cancer cells stimulate stromal fibroblasts (17) and tumor-infiltrating inflammatory cells (18,19) to secrete MMP-9, which in turn contributes to the metastatic activity of the cancer cells. In this model, cancer cells exploit a physiologic mechanism for their metastatic dissemination because stromal cell MMP-9 is central to inflammation (20) and wound healing (21,22).…”

mentioning

confidence: 99%

Tumor Epithelial Cell Matrix Metalloproteinase 9 Is a Target for Antimetastatic Therapy in Colorectal Cancer

Lubbe

Zhou

et al. 2006

Clinical Cancer Research

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Background: The current paradigm suggests that matrix metalloproteinase 9 expressed by stromal cells is a therapeutic target in human colorectal tumors which presumably regulates metastatic disease progression. Conversely, whereas cancer cells within those tumors may induce stromal cells to produce MMP-9 and may be targets for MMP-9 activity, they are not the source of MMP-9 underlying metastasis. Methods: MMP-9 expression in matched colorectal tumors and normal adjacent mucosa from patients and human colon cancer cell lines was examined by real-time reverse transcription-PCR, laser capture microdissection, immunoelectron microscopy, and immunoblot analysis. The role of colon cancer cell MMP-9 in processes underlying metastasis was explored in vitro by examining degradation of extracellular matrix components by gelatin zymography and formation of locomotory organelles by cell spreading analysis and in vivo by quantifying hematogenous tumor cell seeding of mouse lungs. Results: Primary colorectal tumors overexpress MMP-9 compared with matched normal adjacent mucosa. In contrast to the current paradigm, MMP-9 is expressed equally by cancer and stromal cells within human colon tumors. Cancer cell MMP-9 regulates metastatic behavior in vitro, including degradation of extracellular matrix components and formation of locomotory organelles. Moreover, this MMP-9 critically regulates hematogenous seeding of mouse lungs by human colon cancer cells in vivo. Conclusions: These observations reveal that MMP-9 produced by human colon cancer, rather than stromal, cells is central to processes underlying metastasis. They underscore the previously unrecognized potential of specifically targeting tumor cell MMP-9 in interventional strategies to reduce mortality from metastatic colorectal cancer.Colorectal cancer, one of the most prevalent cancers worldwide (1), is the second leading cause of cancer-related mortality in developed countries (1 -4). Whereas mortality (rate, f50%) can be prevented by surgical resection of the involved bowel before tumor cell dissemination (2 -5), f61% of patients have metastatic disease at presentation (Fig. 1A, inset) and f90% of those patients die within 5 years of diagnosis ( Fig. 1A; ref. 2). Moreover, adjuvant chemotherapy for metastatic colorectal cancer increases median survival by only f14 months (6). These observations highlight the unmet need for rationally designed targeted therapeutic interventions to manage the metastatic process in colorectal cancer patients.Matrix metalloproteinase 9 (MMP-9) is a zinc-dependent extracellular protease which regulates metastatic progression in colorectal cancer (7 -9). Also termed the 92-kDa type IV collagenase or gelatinase B, MMP-9 degrades basement membrane collagen type IV, allowing epithelial cancer cells to invade the adjacent stromal compartment (10, 11). MMP-9 promotes cancer progression by regulating physiologically based processes co-opted during metastasis, including cell adhesion, migration, tissue invasion, intravasation and extrava...

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Spectrum of matrix metalloproteinase expression in primary and metastatic colon cancer: relationship to the tissue inhibitors of metalloproteinases and membrane type-1-matrix metalloproteinase

Cited by 54 publications

References 23 publications

Small Integrin Binding Ligand N -Linked Glycoprotein Gene Family Expression in Different Cancers

Small Integrin Binding Ligand N -Linked Glycoprotein Gene Family Expression in Different Cancers

Matrix Metalloproteinase-2 (-1306 C>T) Promoter Polymorphism and Risk of Colorectal Cancer in the Saudi Population

Tumor Epithelial Cell Matrix Metalloproteinase 9 Is a Target for Antimetastatic Therapy in Colorectal Cancer

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