Extracellular Matrix Induced Integrin Signal Transduction and Breast Cancer Invasion
Final rept. 1 Oct 94-30 Nov 97
VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
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Breast epithelial cell function is greatly influenced by interactions with the underlying basal lamina. Matrilysin, a matrix metalloproteinase, has previously been shown to be expressed in both adenomas and carcinomas of the human breast. We have tested the hypothesis that cell-ECM interactions regulate the expression of matrilysin in human breast carcinoma cells in vitro. We have used northern analysis and in situ hybridization to determine levels and localization of several members of the MMP family in human tumors implanted into nude mouse mammary glands. Tumors from mammary glands injected with the human breast adenocarcinoma cell line MDA-MB-468 were shown to express matrilysin a MMP that is primarily expressed in normal and neoplastic cells of epithelial origin. Stromelysin-1 was induced in the stroma of the host mammary gland in the region immediately surrounding the tumor. Northern analysis revealed that gelatinase A, which - was not produced by MDA-MB-468 in vitro. was expressed in the tumor. This combination of MMPs along with stromelysin-3, which has been extensively studied in breast cancer. may lead to the eventual metastasis of mammary tumors to the regional lymph nodes and distant sites. We also describe a new antibody against human matrilysin which indicates that matrilysin is expressed in epithelial cells as expected and appears to be apically secreted in endometrium, Breast and prostate. This lumenal secretion of an MMP that degrades extracellular matrix molecules may have important implications as to its function in normal and neoplastic tissues.
- Anatomy and Physiology
- Medicine and Medical Research