+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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



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



British Journal of Cancer 84(12): 1664-1670



The matrix metalloproteinases, MMP-2 and MMP-9, are capable of degrading components of the basement membrane, a vital barrier breached during the progression of colorectal cancer. The regulation of MMP-2 activation and subsequent targets is vital to understanding the metastatic process. MMP-2 was not expressed by colorectal cancer cells (C170 and C170HM(2)) in vitro but by stromal fibroblasts (46BR.1GI). There was induction of this MMP upon transwell co-cultivation of the colon cancer cells with the fibroblasts but in vivo growth did not lead to a similar increase in the metastatic tumour cells (C170HM(2)), MMP-2 again being attributed to the stromal cells. MMP-2 mRNA was overexpressed in human colorectal tumours compared to normal colorectal tissue, which correlated with Dukes' stage and immunolocalized to the stromal compartment of the tumour tissue. The active form of the MMP-2 enzyme was also present in the colorectal tumour tissue (7/8) but essentially absent in all normal colon samples examined (1/8). MMP-2 activation was not related to an increase in MT-1-MMP mRNA or a decrease in the specific inhibitor TIMP-2 in human tissue. There was however an increase in MMP-2/TIMP-2 ratio in tumour compared to normal. MMP-9, a target of active MMP-2, was present in the metastatic cell line but expression was down-regulated in the tumour cells in vivo, gelatin analysis revealed that MMP-9 was almost entirely attributable to the murine host, confirmed by PCR. There was no increase in mRNA for MMP-9 or its specific inhibitor TIMP-1 in colorectal tumour tissue compared to normal, MMP-9 protein localized to the inflammatory infiltrate. Fibroblast cells may provide malignant epithelial cells with a ready source of enzyme which is crucial to the metastatic process.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 011386973

Download citation: RISBibTeXText

PMID: 11401321

DOI: 10.1054/bjoc.2001.1831


Related references

Coordinate expression of membrane type-matrix metalloproteinases-2 and 3 (MT2-MMP and MT3-MMP) and matrix metalloproteinase-2 (MMP-2) in primary and metastatic melanoma cells. European Journal of Dermatology 11(5): 420-423, 2001

Analysis of tissue inhibitor of metalloproteinases-2 effect on pro-matrix metalloproteinase-2 activation by membrane-type 1 matrix metalloproteinase using baculovirus/insect-cell expression system. Biochemical Journal 345 Pt 3: 511-519, 2000

Regulation of matrix metalloproteinase-2 , membrane-type matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases-2 expression by elastin-derived peptides in human HT-1080 fibrosarcoma cell line. Clinical & Experimental Metastasis 16(6): 489-500, 1998

Regulation of matrix metalloproteinase-2 (gelatinase A, MMP-2), membrane-type matrix metalloproteinase-1 (MT1-MMP) and tissue inhibitor of metalloproteinases-2 (TIMP-2) expression by elastin-derived peptides in human HT-1080 fibrosarcoma cell line. Clinical and Experimental Metastasis 16(6): 489-500, 1999

Matrix metalloproteinases in human gliomas Activation of matrix metalloproteinase-2 may be correlated with membrane-type-1 matrix metalloproteinase expression. Journal of Korean Medical Science 15(3): 309-314, 2000

Clinical Investigation of Matrix Metalloproteinases, Tissue Inhibitors of Matrix Metalloproteinases, and Matrix Metalloproteinase/Tissue Inhibitors of Matrix Metalloproteinase Complexes and Their Networks in Apical Periodontitis. Journal of Endodontics 42(7): 1082-1088, 2017

Expression of membrane type 1 matrix metalloproteinase, matrix metalloproteinase 2 and tissue inhibitor of metalloproteinase 2 in human cartilaginous tumors with special emphasis on mesenchymal and dedifferentiated chondrosarcoma. Journal of Cancer Research & Clinical Oncology 125(10): 541-548, 1999

Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinase in uterine endometrial carcinoma and a correlation between expression of matrix metalloproteinase-7 and prognosis. International Journal of Molecular Medicine 16(4): 541-546, 2005

Tissue inhibitor of matrix metalloproteinase-2 regulates matrix metalloproteinase-2 activation by modulation of membrane-type 1 matrix metalloproteinase activity in high and low invasive melanoma cell lines. Journal of Biological Chemistry 274(30): 21056-21062, 1999

Membrane-type-1 matrix metalloproteinase, matrix metalloproteinase 2, and tissue inhibitor of matrix proteinase 2 in prostate cancer: identification of patients with poor prognosis by immunohistochemistry. Human Pathology 39(5): 731-739, 2008

Host expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in normal colon tissue affects metastatic potential of colorectal cancer. Diseases of the Colon and Rectum 42(3): 393-397, 1999

Implication of collagen type I-induced membrane-type 1-matrix metalloproteinase expression and matrix metalloproteinase-2 activation in the metastatic progression of breast carcinoma. Laboratory Investigation; A Journal of Technical Methods and Pathology 76(5): 651-660, 1997

The membrane-type-matrix metalloproteinase/matrix metalloproteinase-2/tissue inhibitor of metalloproteinase-2 system in periprosthetic connective-tissue remodeling in loose total-hip prostheses. Laboratory Investigation; A Journal of Technical Methods and Pathology 78(6): 735-742, 1998

Quantitative analysis of gene expressions of matrix metalloproteinase 2 , tissue inhibitor of metalloproteinase 2 , and membrane type matrix metalloproteinase in human bladder cancers. Journal of Urology 157(4 SUPPL ): 148, 1997

Expression of membrane-type matrix metalloproteinase in rabbit neointimal tissue and its correlation with matrix-metalloproteinase-2 activation. Journal of Vascular Research 35(1): 45-54, 1998