The involvement of the cell matrix receptors, or VLA integrins, in the morphogenetic behavior of normal and malignant cells is gradually being uncovered.
The VLA-Integrins are members of a family of cell surface receptors that recognize Arg-Gly-Asp containing ligands and that allow cells to bind extracellular matrix molecules such as fibronectin, laminin, and collagens. These interactions reorganize the topographic distribution of the receptors at the cell surface and are relayed to the cytoplasm and even to the cell nucleus. Coordinated organization of the intracellular cytoskeleton, cell spreading on the matrix, and movement of the cells along concentration gradients of these matrix molecules are the result of these interactions. Evidence exists that the migration of embryonic cells, platelet activation on endothelial defects, and the invasion of fibroblasts, lymphoid cells, and epithelial cells during wound healing are facilitated by Integrin-matrix interactions. Moreover, deficiency in the synthesis of a particular Integrin subunit or the inappropriate expression of one or a few members of this family might contribute fundamentally to invasion and metastasis of malignant cells. Although extensive information is available on the structure of the common beta 1 subunit and on the function of the fibronectin receptor, in particular, the other five members of the very late antigen family, their respective alpha subunits and their function as cell surface receptors remain poorly understood. The rationale for having at least six different receptors on some cells, how they might collaborate, and to what end remains unknown. Finally, the interaction of these cell surface receptors and the modulation of their affinity for their ligand by other cell surface or extracellular matrix components such as heparan sulfate, gangliosides a.o. have been barely touched upon. It can be predicted that these molecules and their interaction with the extracellular matrix will provide a key to the understanding of many normal and malignant morphogenetic cellular properties.
Cassiman
J J
JJ
Center for Human Genetics, University of Leuven, Belgium.
D000595:Amino Acid Sequence; D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics*; D000954:Antigens, Surface / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D002874:Chromosome Mapping; D006801:Humans; D016023:Integrins; D008562:Membrane Glycoproteins / Q000235:genetics*; D016029:Receptors, Very Late Antigen
D000943:Antigens, Differentiation; D000954:Antigens, Surface; D016023:Integrins; D008562:Membrane Glycoproteins; D016029:Receptors, Very Late Antigen