Role of Tumor Collagenase Stimulating Factor in Breast Cancer Invasion and Metastasis.
Annual rept. 1 Dec 96-30 Nov 97,
STATE UNIV OF NEW YORK AT STONY BROOK RESEARCH FOUNDATION
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Extracellular matrix metalloproteinase inhibitor EMMPRIN, a plasma membrane glycoprotein identified originally in carcinoma cells, is responsible for inducing peritumoral fibroblasts to produce matrix metalloproteinases MMPs, thereby enhancing cancer invasion and metastasis. Recently, it has become apparent that EMMPRlN is also involved in selective normal tissue functions. Using in situ hybridization, we have identified EMMPRIN in breast cancer cells. New monoclonal antibodies to EMMPRlN and MTl-MMP are being employed to further define their immunohistochemical localization in breast cancer. We have characterized the human EMMPRIN gene and have noted a high-degree of conservation with the mouse gene. In the 5 flanking region, three SPi and two AP2 sites were identified in the promoter region. The effect of transfecting human breast cancer cells with EMMPRIN cDNA was explored. Expression of EMMPRIN cDNA by MDA-MB-536 cancer cells resulted in a more malignant phenotype after intramammary injection of tumor cells in nude mice. The effect of EMMPRlN on endothelial secretion of MMPs was explored in vitro. EMMPRIN enhanced endothelial cell production of stromelysin- 1, collagenase, and gelatinase A. These data support a role for EMMPRIN in cancer dissemination. The mechanism of action and regulation of EMMPRIN in malignant tissue remain to be examined.
- Medicine and Medical Research