Host-derived tumor endothelial marker 8 promotes the growth of melanoma.
Host-derived tumor endothelial marker 8 promotes the growth of melanoma.
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DOI：
10.1158/0008-5472.can-09-1086
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发表时间：
2009-08-01
期刊：
影响因子：
11.2
通讯作者：
St Croix B
中科院分区：
文献类型：
--
作者：
Cullen M;Seaman S;Chaudhary A;Yang MY;Hilton MB;Logsdon D;Haines DC;Tessarollo L;St Croix B
TEM8最初被鉴定为在人类肿瘤血管系统中过度表达的基因，随后又被鉴定为炭疽毒素受体。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的TEM8基因。TEM8 - / - 小鼠能够存活并成年，在生理性血管生成方面没有缺陷。然而，组织病理学分析显示，在包括卵巢、子宫、皮肤和门齿的牙周韧带等几种组织中存在过多的细胞外基质（ECM），后者导致牙齿发育不良。当用B16黑色素瘤进行攻击时，TEM8 - / - 小鼠的肿瘤生长延迟，而其他肿瘤（如Lewis肺癌）的生长未受影响。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拮抗剂可能在开发新的抗癌疗法中有用。
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 physiological angiogenesis. However, histopathologic analysis revealed an excess of extracellular matrix (ECM) 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 while the growth of other tumors, such as Lewis lung carcinoma, was unaltered. These studies demonstrate that host-derived TEM8 promotes the growth of certain tumors and suggest that TEM8 antagonists may have utility in the development of new anti-cancer therapies.