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 (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.
Reeves
C V
CV
Columbia University Medical Center, New York, NY 10035, USA.
Dufraine
J
J
Young
J A T
JA
Kitajewski
J
J
D000818:Animals; D001940:Breast / Q000098:blood supply / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D002196:Capillaries / Q000166:cytology / Q000254:growth & development / Q000473:pathology; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism / Q000473:pathology*; D004727:Endothelium / Q000254:growth & development; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis / Q000235:genetics; D009369:Neoplasms / Q000098:blood supply* / Q000235:genetics* / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics; D018000:Receptors, Peptide / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
C523013:Antxr2 protein, mouse; D018000:Receptors, Peptide