Cell Matrix interactions are important regulatory events during embryogenesis and repair. From in vitro studies using purified components, a better understanding of how cells adhere, migrate, proliferate, and differentiate in response to tissue and cell-specific matrix molecules has been established. We have found that the basement membrane, the extracellular which underlies all epithelial cells and endothelial cells and surrounds muscle cells, promotes cell differentiation in vitro. Endothelial cells form capillary-like structures with a lumen, Sertoli cells form cord-like structures, bone cells form canaliculi, glandular cells form glands, etc. Our goal is to define the molecular and cellular events involved in this process. Our approach has been to identify the (1) biologically active matrix components, (2) localize active sites on the matrix component with site specific antibodies and synthetic peptides, (3) identify and characterize cellular receptors, (4) gain an understanding of the intracellular events involved in the biological response, and (5) identify genes induced by the extracellular matrix. Specifically, we have identified five active sites on the basement membrane glycoprotein laminin. These peptides are active for cell adhesion, migration, neurite outgrowth, collagen IV production, and promotion and inhibition of tumor metastases. Such peptides have potential as therapeutic agents. We have also found that the intracellular signalling events in response to laminin involve dephosphorylation for nerve cells and phosphorylation for endothelial cells. The cellular receptors are distinct.
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