Anthrax Toxin Receptor 2 is expressed in murine and tumor vasculature and functions in endothelial proliferation and morphogenesis

The Capillary Morphogenesis Gene 2 (CMG2) gene encodes an Anthrax toxin receptor (ANTXR2) but the normal physiological function is not known. ANTXR2/CMG2 was originally identified as a result of up-regulation during capillary morphogenesis of endothelial cells cultured in vitro. We explored the hypothesis that key steps of the angiogenic process are either dependent or are influenced by ANTXR2/CMG2 activity. We describe the expression pattern of ANTXR2/CMG2 in several murine tissues and in normal breast and breast tumors. Endothelial expression was found in all of the tissues analyzed, in cultured endothelial cells and in breast tumor vessels; however ANTXR2/CMG2 expression was not restricted to this cell type. To assess potential angiogenic function, we utilized RNA interference to achieve significant reduction of ANTXR2/CMG2 expression in cultured human umbilical venous endothelial cells. Reduced ANTXR2/CMG2 expression resulted in significant inhibition of proliferation and reduced capacity of endothelial cells to form capillary-like networks in vitro, while overexpression of ANTXR2/CMG2 in HUVEC increased proliferation and capillary-like network formation. Little change in migration of endothelial cells was observed upon knockdown or overexpression. We conclude that ANTXR2/CMG2 functions to promote endothelial proliferation and morphogenesis during sprouting angiogenesis, consistent with the endothelial expression of ANTXR2/CMG2 in several vascular beds.