PMID: 8983067Jan 1, 1994Paper

Cell adhesion and tumor metastasis

Princess Takamatsu Symposia
E Ruoslahti

Abstract

Integrins, among the various classes of cell adhesion receptors, are particularly associated with cell adhesion to extracellular matrices. They are heterodimeric transmembrane proteins with large ectodomains and short cytoplasmic tails. In many cases the sequence recognized by the integrins in the extracellular matrix proteins is the tripeptide Arg-Gly-Asp (RGD). Short synthetic peptides containing this sequence can inhibit tumor cell invasion in vitro and tumor dissemination in vivo. Because the alpha 5 beta 1 integrin appears to be the target of the peptides in many types of tumors, we have used phage display libraries to analyze the specificity of alpha 5 beta 1 and have isolated potent and specific inhibitors for this integrin. Increased expression of the alpha 5 beta 1 integrin, which is a fibronectin receptor, can also suppress cell migration and tumor cell invasion. We suggest this effect may be mediated through increased deposition of fibronectin matrix around the cells, because we found that the fibrillar matrix fibronectin suppresses tumor cell migration. There is increasing evidence that signals are elicited by the binding of integrins to their target proteins. This possibility has generated a great deal of interest ...Continue Reading

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