title: Endosialin/TEM 1/CD248 is a pericyte marker of embryonic and tumor neovascularization.
abstract: The formation of functional, mature blood vessels depends on the interaction between endothelial cells and pericytes. Commonality exists in the processes involved in vasculature development between tissues whether healthy or diseased. Endosialin/TEM 1 is a cell membrane protein that is expressed in blood vessels during embryogenesis and tumorigenesis but not in normal mature vessels. Antibodies developed to human endosialin were used to investigate endosialin expression and function in human prenatal brain pericytes and pericytes residing in tumors. Anti-endosialin was capable of preventing pericyte tube formation in culture and inhibited migration. Brain pericytes in culture had higher levels of endosialin/TEM 1 than TEMs-2, -3, -4, -5, -7, and -8. Immunocytochemistry revealed that endosialin was present in the cytoplasmic body and in the elongated extensions essential to pericyte function. Transgenic mice engineered to express human endosialin bred on an immunocompromised background allowed the growth of human tumor xenografts. In human colon carcinoma Colo205 and HT29 xenografts grown in human endosialin-transgenic mice, endosialin expression was largely confined to NG2-expressing perivascular cells and not CD31-positive endothelial cells. Similar methods applied to human ovarian and colon tumors confirmed endosialin expression by pericytes. The data indicate that endosialin is strongly expressed by pericytes during periods of active angiogenesis during embryonic and tumor development. Anti-endosialin antibodies may have value in identifying vasculature in malignant tissues. With the appropriate agent, targeting endosialin may interfere with blood vessel growth during tumor development.
authors.affiliation: Genzyme Corporation, 49 New York Avenue Framingham, MA 01701-9322, USA. Rebecca.Bagley@Genzyme.com
authors.forename: Rebecca G
authors.initials: RG
authors.lastname: Bagley
authors.forename: Nakayuki
authors.initials: N
authors.lastname: Honma
authors.forename: William
authors.initials: W
authors.lastname: Weber
authors.forename: Paula
authors.initials: P
authors.lastname: Boutin
authors.forename: Cecile
authors.initials: C
authors.lastname: Rouleau
authors.forename: Srinivas
authors.initials: S
authors.lastname: Shankara
authors.forename: Shiro
authors.initials: S
authors.lastname: Kataoka
authors.forename: Isao
authors.initials: I
authors.lastname: Ishida
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Roberts
authors.forename: Beverly A
authors.initials: BA
authors.lastname: Teicher