The extracellular matrix has been found to be important in embryogenesis and in 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 matrix which underlies all epithelial cells and endothelial cells and surrounds nerve cells, promotes cell differentiation in vitro. Endothelial cells form capillary-like structures with a lumen, bone cells form canaliculi, salivary 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 defined YIGSR as an antiangiogenic site on laminin and SIKVAV as an angiogenic and neurite promoting site. Two new angiogenic factors, scatter factor and haptoglobin, were defined using in vitro and in vivo assays developed by us. In addition, estrogens have been found to promote angiogenesis on basement membrane and to increase leukocyte-endothelial cell adhesion. A brain derived cellular receptor for SIKVAV shares homology with the amyloid precursor protein and may define the role of this protein in development and in Alzheimer's disease. Subtractive cDNA cloning of endothelial cells on plastic vs basement membrane has identified several novel genes as well as thymosin and calmodulin as induced during differentiation into vessels.
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