1. ¹OB/GYN, Columbia University Medical Center, New York, NY, USA
2. ²Department of Pathology, Irving Cancer Research Center, Columbia University Medical Center, New York, NY, USA
3. ³Infectious Disease Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA
4. ⁴Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA

Correspondence: Dr J Kitajewski, Department of Pathology, Irving Cancer Research Center, Office 926, Columbia University, 1130 St Nicholas Avenue, New York, NY 10035, USA. E-mail: jkk9@columbia.edu

Received 11 December 2008; Revised 18 September 2009; Accepted 28 September 2009; Published online 9 November 2009.

Abstract

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 (ECs) 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 ECs and in breast tumor vessels; however, ANTXR2/CMG2 expression was not restricted to this cell type. To assess potential angiogenic function, we used RNA interference to achieve significant reduction of ANTXR2/CMG2 expression in cultured human umbilical venous endothelial cells (HUVECs). Reduced ANTXR2/CMG2 expression resulted in significant inhibition of proliferation and reduced capacity of ECs to form capillary-like networks in vitro, whereas overexpression of ANTXR2/CMG2 in HUVEC increased proliferation and capillary-like network formation. Little change in migration of ECs was observed on 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.