Double target for tumor mass destruction.

Abstract

As the growth of most cancers is dependent on the growth of tumor blood vessels, inhibition of tumor angiogenesis may provide an efficient strategy to slow down or block tumor growth. The possibility of selectively targeting angiogenic vasculature in a tumor mass depends on molecular, cellular, and structural differences between the tumor vessels and their normal counterparts (Figure ​(Figure1).1). Tumor cells, like normal cells, need to be located close to the blood vessels serving their metabolic demands to the extent that in solid tumors every endothelial cell in a tumor vessel is considered to support several concentric layers of tumor cells (1). A hypoxic tumor generates its own microcirculation mainly via the hypoxia-inducible factor (HIF) complex, which is activated by inhibition of its oxygen-dependent prolyl hydroxylation and proteasomal destruction (2). This leads to increased transcription of several hypoxia-induced genes. One such gene encodes VEGF, which activates endothelial cell (EC) responses during angiogenesis in coordination with, for example, matrix adhesion events. Studies of the signaling pathways of VEGF receptors, integrins, and cadherins have provided new antiangiogenic strategies for inhibition of tumor growth, and inhibition of VEGF-C and VEGF-D signals that stimulate lymphangiogenesis seems to inhibit lymphatic metastasis in mice (3). One of the most striking new developments in antiangiogenesis research concerns the inflammatory cells and pericytes (PCs) associated with the tumor vasculature. The new findings presented in this issue of the JCI by Bergers and collaborators suggest that the PCs of tumor blood vessels and their signaling mechanisms via the PDGFR-β are functionally important for the maintenance of tumor blood vessels (4). These findings add another constituent cell type of tumor stroma to the list of anticancer targets. Figure 1 Growth factor receptor signals involved in tumor angiogenesis and vascular development. A solid tumor is dependent on new blood vessels for growth. (a) Angiogenesis is induced by VEGF produced mainly by hypoxic tumor cells and inflammatory cells (such ...