Host-derived tumor endothelial marker 8 promotes the growth of melanoma.
Tumor endothelial marker 8 (TEM8) was initially identified as a gene overexpressed in the vasculature of human tumors and was subsequently identified as an anthrax toxin receptor. To assess the functional role of TEM8, we disrupted the TEM8 gene in mice by targeted homologous recombination. TEM8(-/-) mice were viable and reached adulthood without defects in physiologic angiogenesis. However, histopathologic analysis revealed an excess of extracellular matrix in several tissues, including the ovaries, uterus, skin, and periodontal ligament of the incisors, the latter resulting in dental dysplasia. When challenged with B16 melanoma, tumor growth was delayed in TEM8(-/-) mice, whereas the growth of other tumors, such as Lewis lung carcinoma, was unaltered. These studies show that host-derived TEM8 promotes the growth of certain tumors and suggest that TEM8 antagonists may have utility in the development of new anticancer therapies.
Cullen
Mike
M
Tumor Angiogenesis Section, Mouse Cancer Genetics Program, Science Applications International Corporation, National Cancer Institute-Frederick, Frederick, Maryland 21702-1201, USA.
Seaman
Steven
S
Chaudhary
Amit
A
Yang
Mi Young
MY
Hilton
Mary Beth
MB
Logsdon
Daniel
D
Haines
Diana C
DC
Tessarollo
Lino
L
St Croix
Brad
B
D000818:Animals; D014408:Biomarkers, Tumor; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D005260:Female; D008297:Male; D008546:Melanoma, Experimental / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins; D009389:Neovascularization, Pathologic / Q000473:pathology; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
C523012:Antxr1 protein, mouse; D014408:Biomarkers, Tumor; D008840:Microfilament Proteins; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide