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.

Endosialin, alternatively named tumor endothelial marker or CD248, was originally discovered as an antigen selectively expressed in tumor blood vessels. Subsequent studies showed that it is confined to stromal fibroblasts and pericytes of tumor vasculature rather than to tumor endothelium. Endosialin levels are upregulated in different tumor types including those derived from the brain, colon and breast. Expression of endosialin is associated with tumor growth, progression and correlates with a pro-proliferative and promigratory phenotype. However, the function of endosialin and mechanisms of its regulation are still incompletely understood. To facilitate further study of endosialin in angiogenesis, its interaction with the potential binding partners and other aspects of endosialin function, we generated six new domainspecific anti-endosialin monoclonal antibodies. Two of them recognize the C-type lectin-like domain-Sushi/SCR/CCP and four antibodies are directed to the sialomucin domain. The antibodies are suitable for various immunodetection methods including immunoblotting and immunohistochemistry. They represent important tools for improving our understanding of endosialin regulation, biological role and contribution of its extracellular domains to the tumor phenotype.