PDGF and PDGF receptors in glioma

Abstract

The family of platelet-derived growth factors (PDGFs) plays a number of critical roles in normal embryonic development, cellular differentiation, and response to tissue damage. Not surprisingly, as it is a multi-faceted regulatory system, numerous pathological conditions are associated with aberrant activity of the PDGFs and their receptors. As we and others have shown, human gliomas, especially glioblastoma, express all PDGF ligands and both the two cell surface receptors, PDGFR-α and -β. The cellular distribution of these proteins in tumors indicates that glial tumor cells are stimulated via PDGF/PDGFR-α autocrine and paracrine loops, while tumor vessels are stimulated via the PDGFR-β. Here we summarize the initial discoveries on the role of PDGF and PDGF receptors in gliomas and provide a brief overview of what is known in this field.

Figure 1.

Receptor binding specificity of five dimeric PDGF ligands. *Ligand DD can activate αβ with lower specificity.

Figure 2.

Three possible ways for a cancer stem cell (CSC) to arise: a neural stem cell (NCS) acquires a mutation; a progenitor cell (PC) acquires two or more mutations; or a fully differentiated cell (DC) undergoes several mutations that transform and drive it back to a stem-like state.