Cullen Mike, Seaman Steven, Chaudhary Amit, Yang Mi Young, Hilton Mary Beth, Logsdon Daniel, Haines Diana C, Tessarollo Lino, St Croix Brad
Tumor Angiogenesis Section, Mouse Cancer Genetics Program, Science Applications International Corporation, National Cancer Institute-Frederick, Frederick, Maryland 21702-1201, USA.
Cancer Res. 2009 Aug 1;69(15):6021-6. doi: 10.1158/0008-5472.CAN-09-1086. Epub 2009 Jul 21.
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.
肿瘤内皮标志物8（TEM8）最初被鉴定为在人类肿瘤脉管系统中过度表达的一种基因，随后被确定为炭疽毒素受体。为了评估TEM8的功能作用，我们通过靶向同源重组破坏了小鼠中的TEM8基因。TEM8基因敲除（TEM8(-/-)）小鼠存活下来并成年，生理性血管生成无缺陷。然而，组织病理学分析显示，包括卵巢、子宫、皮肤和切牙的牙周韧带在内的多个组织中细胞外基质过多，后者导致牙齿发育异常。当用B16黑色素瘤攻击时，TEM8(-/-)小鼠的肿瘤生长延迟，而其他肿瘤如Lewis肺癌的生长未改变。这些研究表明，宿主来源的TEM8促进某些肿瘤的生长，并提示TEM8拮抗剂可能在新型抗癌疗法的开发中具有应用价值。
