Endosialin: molecular and functional links to tumor angiogenesis

Endosialin, alternatively named tumor endothelial marker 1 (TEM1) or CD248, is a bulk transmembrane glycoprotein expressed both in developing and adult tissues undergoing active physiological or pathological angiogenesis. Endosialin is often overexpressed in tumors, particularly in stromal cells and in vessels-covering pericytes, and its transcription is induced by hypoxia via HIF-2 transcription factor. Based on the expression pattern, molecular characteristics and phenotypes of genetic models, endosialin has been proposed to function as a receptor implicated in sprouting angiogenesis, vasculogenesis and/or pruning of vessels. Here we provide an overview of the recent knowledge linking endosialin to diverse aspects of angiogenesis. Based on data-mining, our experimental data and available literature, we suggest that endosialin cross-talks with both pro- and anti-angiogenic signals and ECM components, and participates in dynamic vascular remodeling, which facilitates tumor growth. Tumor-selective targeting of endosialin may therefore contribute to improvement of existing anti-angiogenic therapies.