This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Bagley, R. G. Articles by Teicher, B. A. PubMed PubMed Citation Articles by Bagley, R. G. Articles by Teicher, B. A.

Research Articles: Therapeutics, Targets, and Development

Human endothelial precursor cells express tumor endothelial marker 1/endosialin/CD248

¹ Genzyme Corporation, Framingham, Massachusetts and ² Kirin Pharma Co., Ltd., Gunma, Japan

Requests for reprints: Rebecca G. Bagley, Genzyme Corporation, 49 New York Avenue, Framingham, MA 01701-9322. Phone: 508-270-2455; Fax: 508-271-4796. E-mail: Rebecca.Bagley{at}Genzyme.com

Abstract

Angiogenesis occurs during normal physiologic processes as well as under pathologic conditions such as tumor growth. Serial analysis of gene expression profiling revealed genes [tumor endothelial markers (TEM)] that are overexpressed in tumor endothelial cells compared with normal adult endothelial cells. Because blood vessel development of malignant tumors under certain conditions may include endothelial precursor cells (EPC) recruited from bone marrow, we investigated TEM expression in EPC. The expression of TEM1 or endosialin (CD248) and other TEM has been discovered in a population of vascular endothelial growth factor receptor 2⁺/CD31⁺/CD45^–/VE-cadherin⁺ EPC derived from human CD133⁺/CD34⁺ cells. EPC share some properties with fully differentiated endothelial cells from normal tissue, yet reverse transcription-PCR and flow cytometry reveal that EPC express higher levels of endosialin at the molecular and protein levels. The elevated expression of endosialin in EPC versus mature endothelial cells suggests that endosialin is involved in the earlier stages of tumor angiogenesis. Anti-endosialin antibodies inhibited EPC migration and tube formation in vitro. In vivo, immunohistochemistry indicated that human EPC continued to express endosialin protein in a Matrigel plug angiogenesis assay established in nude mice. Anti-endosialin antibodies delivered systemically at 25 mg/kg were also able to inhibit circulating murine EPC in nude mice bearing s.c. SKNAS tumors. EPC and bone marrow–derived cells have been shown previously to incorporate into malignant blood vessels in some instances, yet they remain controversial in the field. The data presented here on endothelial genes that are up-regulated in tumor vasculature and in EPC support the hypothesis that the angiogenesis process in cancer can involve EPC. [Mol Cancer Ther 2008;7(8):2536–46]