The role of integrins in the malignant phenotype of gliomas.

Abstract

Integrins are cell surface receptors that mediate the physical and functional interactions between a cell and its surrounding extracellular matrix (ECM). Expressed as heterodimers, the specific alpha or beta chains that constitute the integrin receptor determine the repertoire of ECM proteins to which a specific integrin may bind (table 1). While classically, the role ascribed to integrins has been that of anchoring cells to the ECM, the more contemporary spectrum of integrin function greatly exceeds that of mere cell adhesion. Recent reports have demonstrated that the interaction between the ECM and cell surface integrins leads to intracellular signaling events that affect cell migration, proliferation, and survival, which in the context of neoplastic cells, can translate directly into the malignant phenotype (1). Indeed, the role of specific integrins in tumorigenesis has been demonstrated in numerous cancer types (table 2). In primary tumors of the nervous system, the contribution of integrins to the malignant phenotype of gliomas has been an area of significant attention and research in numerous laboratories, including that of ours. As illustrated in table 3, several integrins have been identified as being of key importance in glioma biology. In this article, we review the current knowledge of how these integrins influence the malignant characteristics of gliomas and, as such, how these cell surface receptors may thus represent potential targets in the design of future therapeutics for patients afflicted with gliomas.