Host-Derived Tumor Endothelial Marker 8 Promotes the Growth of Melanoma

• Published in: Cancer research (Chicago, Ill.) Vol. 69; no. 15; pp. 6021 - 6026
• Main Authors: CULLEN, Mike, SEAMAN, Steven, CHAUDHARY, Amit, MI YOUNG YANG, HILTON, Mary Beth, LOGSDON, Daniel, HAINES, Diana C, TESSAROLLO, Lino, CROIX, Brad St
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.08.2009
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Biomarkers, Tumor; Carcinoma, Lewis Lung - blood supply; Carcinoma, Lewis Lung - metabolism; Carcinoma, Lewis Lung - pathology; Dermatology; Female; Male; Medical sciences; Melanoma, Experimental - blood supply; Melanoma, Experimental - metabolism; Melanoma, Experimental - pathology; Mice; Mice, Inbred C57BL; Mice, Knockout; Microfilament Proteins; Neovascularization, Pathologic - pathology; Pharmacology. Drug treatments; Receptors, Cell Surface; Receptors, Peptide - biosynthesis; Receptors, Peptide - deficiency; Receptors, Peptide - genetics; Receptors, Peptide - physiology; Tumors; Tumors of the skin and soft tissue. Premalignant lesions; TEM8 gene; Malignant tumor; Growth; Malignant melanoma; Cancer
• ISSN: 0008-5472; 1538-7445; 1538-7445
• DOI: 10.1158/0008-5472.CAN-09-1086

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.