title: TEM8/ANTXR1 blockade inhibits pathological angiogenesis and potentiates tumoricidal responses against multiple cancer types.
abstract: Current antiangiogenic agents used to treat cancer only partially inhibit neovascularization and cause normal tissue toxicities, fueling the need to identify therapeutic agents that are more selective for pathological angiogenesis. Tumor endothelial marker 8 (TEM8), also known as anthrax toxin receptor 1 (ANTXR1), is a highly conserved cell-surface protein overexpressed on tumor-infiltrating vasculature. Here we show that genetic disruption of Tem8 results in impaired growth of human tumor xenografts of diverse origin including melanoma, breast, colon, and lung cancer. Furthermore, antibodies developed against the TEM8 extracellular domain blocked anthrax intoxication, inhibited tumor-induced angiogenesis, displayed broad antitumor activity, and augmented the activity of clinically approved anticancer agents without added toxicity. Thus, TEM8 targeting may allow selective inhibition of pathological angiogenesis.
authors.affiliation: Tumor Angiogenesis Section, Mouse Cancer Genetics Program, National Cancer Institute (NCI), National Institutes of Health (NIH), Frederick, MD 21702, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Chaudhary
authors.forename: Mary Beth
authors.initials: MB
authors.lastname: Hilton
authors.forename: Steven
authors.initials: S
authors.lastname: Seaman
authors.forename: Diana C
authors.initials: DC
authors.lastname: Haines
authors.forename: Susan
authors.initials: S
authors.lastname: Stevenson
authors.forename: Peter K
authors.initials: PK
authors.lastname: Lemotte
authors.forename: William R
authors.initials: WR
authors.lastname: Tschantz
authors.forename: Xiaoyan M
authors.initials: XM
authors.lastname: Zhang
authors.forename: Saurabh
authors.initials: S
authors.lastname: Saha
authors.forename: Tony
authors.initials: T
authors.lastname: Fleming
authors.forename: Brad
authors.initials: B
authors.lastname: St Croix
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology / Q000633:toxicity; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology; D008545:Melanoma / Q000235:genetics / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D009369:Neoplasms / Q000098:blood supply*; D009389:Neovascularization, Pathologic / Q000235:genetics; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D014183:Transplantation, Heterologous; D014945:Wound Healing / Q000235:genetics
chemical_list: C473287:ANTXR1 protein, human; D007074:Immunoglobulin G; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface