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Extracellular Matrix Induced Integrin Signal Transduction and Breast Cancer Invasion.

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Annual rept. 1 Oct 94-30 Sep 95,

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Breast epithellal cell function is greatly influenced by interactions with the underlying basal lamina. Matrilysin, a matrix metallo-proteinase, 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. The cell line MDA-468 which constitutively expresses matrilysin when plated on plastic was plated various ECM proteins. Northern analysis of cells seeded on RGD peptides, fibronectin, laminin and ECM indicated that matrilysin remained at constitutive levels for 6 hours, but by 20 hours the mRNA declines by at least 50 and reached a nadir of 20 of the initial mRNA levels. Collagen type I inhibited matrilysin production in less than 6 hours and this inhibition was sustained throughout the 48 hour time course. These data indicate that breast tumor cells can regulate matrilysin in response to cues from the ECM as the cells invade the host tissue. We also 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.

Subject Categories:

  • Medicine and Medical Research
  • Anatomy and Physiology
  • Metallurgy and Metallography

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