No abstract

Human melanoma cells required ligation of the integrin a4P3 to sustain viability and growth in threedimensional dermal collagen. Variant melanoma cells, lacking the a, subunit, progressed rapidly to apoptosis within this matrix, whereas transfection of these cells with an a, cDNA restored al3 expression and prevented apoptosis. Furthermore, inhibition of a,(3 ligation with a monoclonal antibody promoted cell death. Apoptosis of a, (-) 8856The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Netrins, axon guidance cues in the CNS, have also been detected in epithelial tissues. In this study, using the embryonic pancreas as a model system, we show that Netrin-1 is expressed in a discrete population of epithelial cells, localizes to basal membranes, and specifically associates with elements of the extracellular matrix. We demonstrate that alpha6beta4 integrin mediates pancreatic epithelial cell adhesion to Netrin-1, whereas recruitment of alpha6beta4 and alpha3beta1 regulate the migration of CK19+/PDX1+ putative pancreatic progenitors on Netrin-1. These results provide evidence for the activation of epithelial cell adhesion and migration by a neural chemoattractant, and identify Netrin-1/integrin interactions as adhesive/guidance cues for epithelial cells.

Collagens have been shown to influence the survival and function of cultured ␤-cells; however, the utilization and function of individual collagen receptors in ␤-cells is largely unknown. The integrin superfamily contains up to five collagen receptors, but we have determined that ␣ 1 ␤ 1 is the primary receptor utilized by both fetal and adult ␤-cells. Cultured ␤-cells adhered to and migrated on collagen type IV (Col-IV), and these responses were mediated almost exclusively by ␣ 1 ␤ 1 . The migration of cultured ␤-cells to Col-IV significantly exceeded that to other matrix components suggesting that this substrate is of unique importance for ␤-cell motility. The interaction of ␣ 1 ␤ 1 with Col-IV also resulted in significant insulin secretion at basal glucose concentrations. A subset of ␤-cells in developing islets was confirmed to express ␣ 1 ␤ 1 , and this expression co-localized with Col-IV in the basal membranes of juxtaposed endothelial cells. Our findings indicate that ␣ 1 ␤ 1 and Col-IV contribute to ␤-cell functions known to be important for islet morphogenesis and glucose homeostasis.