Anthrax toxin receptor 2 is expressed in murine and tumor vasculature and functions in endothelial proliferation and morphogenesis

• Published in: Oncogene Vol. 29; no. 6; pp. 789 - 801
• Main Authors: Reeves, C V, Dufraine, J, Young, J A T, Kitajewski, J
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11-02-2010; Nature Publishing Group
• Subjects: Angiogenesis; Animals; Anthrax; Apoptosis; Bacterial diseases; Biological and medical sciences; Breast - blood supply; Breast - cytology; Breast - metabolism; Breast - pathology; Breast cancer; Capillaries - cytology; Capillaries - growth & development; Capillaries - pathology; Cell Biology; Cell Line; Cell Movement - genetics; Cell physiology; Cell Proliferation; Cell receptors; Cell structures and functions; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cellular biology; Endothelial cells; Endothelial Cells - cytology; Endothelial Cells - metabolism; Endothelial Cells - pathology; Endothelium; Endothelium - growth & development; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation; Gene Knockdown Techniques; Genes; Genetic aspects; Human bacterial diseases; Human Genetics; Humans; Immunohistochemistry; Infectious diseases; Internal Medicine; Medical sciences; Medicine; Medicine & Public Health; Mice; Mice, Inbred C57BL; Miscellaneous; Molecular and cellular biology; Morphogenesis; Morphogenesis - genetics; Neoplasms - blood supply; Neoplasms - genetics; Neoplasms - metabolism; Neovascularization; Neovascularization, Physiologic - genetics; Oncology; original-article; Physiological aspects; Receptors, Peptide - deficiency; Receptors, Peptide - genetics; Receptors, Peptide - metabolism; RNA-mediated interference; Rodents; Tumors; Veins & arteries; United States; endothelial cells; CMG2; ANTXR2; angiogenesis; Cell proliferation; Endothelial cell; Rodentia; Gene expression; Carcinogenesis; Endothelium; Vascularization; Infection; Morphogenesis; Angiogenesis; Toxin; Vertebrata; Mammalia; Mouse; Anthrax; Bacteriosis; Tumor; Biological receptor
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2009.383

The
C
apillary
M
orphogenesis
G
ene 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.