Tumor cell-matrix interaction: pericellular matrix degradation and metastasis.

Abstract

In order to determine key MMPs for invasion and metastasis in various human cancers, we examined the expression of ten MMPs (MMP-1, 2, 3, 7, 8, 9, 13 and MT1, 2, 3-MMPs) and tissue inhibitors of metalloproteinases (TIMP-1 and 2) in breast carcinomas, thyroid papillary carcinomas, endometrial carcinomas, ovarian carcinomas, gastric adenocarcinomas, oral squamous cell carcinomas and gliomas. Of the MMPs examined, the activation of proMMP-2 by MT1-MMP (membrane type 1-MMP) was commonly important for the invasion and metastasis of these cancers except for endometrial carcinomas. The MMP-2 and MT1-MMP were localized to the carcinoma cells and gelatinolytic activity was demonstrated within the carcinoma cell nests by in situ zymography. In endometrial carcinomas, production and activation of proMMP-7 were a key determinant of the lymph node metastasis. The activation of proMMP-2 in gliomas involved MT2-MMP as well as MT1-MMP, and a combination of decreased TIMP-2 production and enhanced MT1-MMP expression was important in the subarachnoidal dissemination of glioblastoma cells. Brevican, a major adult brain proteoglycan, was degraded with MMP-1, 2, 3, 7, 10 and ADAMTS4 (aggrecanase-1) by being cleaved at the MMP site (the Ala360-Phe361 bond) with the MMPs and ADAM site (the Glu395-Ser396 bond) with ADAMTS4. Since activated MMP-2 and ADAMTS4 are present in human glioma tissues, they may play a key role in the invasion of glioma cells through the brevican degradation. The data in the present study suggest that the extracellular matrix-degrading metalloproteinases acting probably on the cell membranes of cancer cells are essential to the invasion and metastasis of human cancers.

• Authors: Y Okada
• Journal: Verhandlungen der Deutschen Gesellschaft fur Pathologie (Verh Dtsch Ges Pathol) Vol. 84 Pg. 33-42 ( 2000) ISSN: 0070-4113 [Print] Germany
• PMID: 11217446 (Publication Type: Journal Article)

Chemical References

• Tissue Inhibitor of Metalloproteinase-1
• Tissue Inhibitor of Metalloproteinase-2
• Matrix Metalloproteinases

Topics

• Extracellular Matrix (pathology, physiology)
• Female
• Humans
• Matrix Metalloproteinases (genetics, metabolism)
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Neoplasms (genetics, pathology, physiopathology)
• Tissue Inhibitor of Metalloproteinase-1 (genetics, metabolism)
• Tissue Inhibitor of Metalloproteinase-2 (genetics, metabolism)
• Tumor Cells, Cultured