title: Tumor endothelial marker 7 (TEM-7): a novel target for antiangiogenic therapy.
abstract: Antiangiogenesis has been validated as a therapeutic strategy to treat cancer, however, a need remains to identify new targets and therapies for specific diseases and to improve clinical benefit from antiangiogenic agents. Tumor endothelial marker 7 (TEM-7) was investigated as a possible target for therapeutic antiangiogenic intervention in cancer. TEM-7 expression was assessed by in situ hybridization or by immunohistochemistry (IHC) in 130 formalin-fixed paraffin-embedded (FFPE) and 410 frozen human clinical specimens of cancer plus 301 normal tissue samples. In vitro TEM-7 expression was evaluated in 4 human endothelial cell models and in 32 human cancer cell lines by RT-PCR and flow cytometry. An anti-TEM-7 antibody was tested in vitro on human SKOV3 ovarian and MDA-MB-231 breast carcinoma cells that expressed TEM-7 in antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis assays. In frozen tumor tissues, TEM-7 mRNA and protein was detected in all but one of the cancer types tested and was infrequently expressed in normal frozen tissues. In FFPE tumor tissues, TEM-7 protein was detected by IHC in colon, breast, lung, bladder, ovarian and endometrial cancers and in sarcomas. TEM-7 protein was not detected in head and neck, prostate or liver cancers. TEM-7 expression was restricted to the vasculature and was absent from tumor cells. In vitro, TEM-7 was not detected in human microvascular endothelial cells (HMVEC) or human umbilical vein endothelial cells (HUVEC) but was induced in endothelial precursor/progenitor cells (EPC) in the presence of the mitogen phorbol ester PMA. An anti-TEM-7 antibody mediated ADCC and phagocytosis in SKOV3 and MDA-MB-231 cell lines infected with an adenovirus expressing TEM-7. These data demonstrate that TEM-7 is a vascular protein associated with angiogenic states. TEM-7 is a novel and attractive target for antiangiogenic therapy.
authors.affiliation: Genzyme Corporation, 49 New York Ave., Framingham, MA 01701, USA. Rebecca.Bagley@Genzyme.com
authors.forename: Rebecca G
authors.initials: RG
authors.lastname: Bagley
authors.forename: Cecile
authors.initials: C
authors.lastname: Rouleau
authors.forename: William
authors.initials: W
authors.lastname: Weber
authors.forename: Khodadad
authors.initials: K
authors.lastname: Mehraein
authors.forename: Robert
authors.initials: R
authors.lastname: Smale
authors.forename: Maritza
authors.initials: M
authors.lastname: Curiel
authors.forename: Michelle
authors.initials: M
authors.lastname: Callahan
authors.forename: Andre
authors.initials: A
authors.lastname: Roy
authors.forename: Paula
authors.initials: P
authors.lastname: Boutin
authors.forename: Thia
authors.initials: T
authors.lastname: St Martin
authors.forename: Mariana
authors.initials: M
authors.lastname: Nacht
authors.forename: Beverly A
authors.initials: BA
authors.lastname: Teicher
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology*; D000920:Antibody-Dependent Cell Cytotoxicity; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D005557:Formaldehyde; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D016612:Paraffin Embedding; D010587:Phagocytosis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016707:Tissue Fixation; D014162:Transfection
chemical_list: D020533:Angiogenesis Inhibitors; D000906:Antibodies; D009363:Neoplasm Proteins; C510620:PLXDC1 protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D005557:Formaldehyde