Nanda Akash, Carson-Walter Eleanor B, Seaman Steven, Barber Thomas D, Stampfl Jason, Singh Sujay, Vogelstein Bert, Kinzler Kenneth W, St Croix Brad
Program in Human Genetics and Molecular Biology and the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland, USA.
Cancer Res. 2004 Feb 1;64(3):817-20. doi: 10.1158/0008-5472.can-03-2408.
Tumor endothelial marker (TEM)8 was uncovered as a gene expressed predominantly in tumor endothelium, and its protein product was recently identified as the receptor for anthrax toxin. Here, we demonstrate that TEM8 protein is preferentially expressed in endothelial cells of neoplastic tissue. We used the extracellular domain of TEM8 to search for ligands and identified the alpha 3 subunit of collagen VI as an interacting partner. The TEM8-interacting region on collagen alpha 3(VI) was mapped to its COOH-terminal C5 domain. Remarkably, collagen alpha 3(VI) is also preferentially expressed in tumor endothelium in a pattern concordant with that of TEM8. These results suggest that the TEM8/C5 interaction may play an important biological role in tumor angiogenesis.
肿瘤内皮标志物(TEM)8被发现是一种主要在肿瘤内皮中表达的基因,其蛋白产物最近被鉴定为炭疽毒素的受体。在此,我们证明TEM8蛋白在肿瘤组织的内皮细胞中优先表达。我们利用TEM8的细胞外结构域寻找配体,并确定胶原蛋白VI的α3亚基为相互作用伴侣。胶原蛋白α3(VI)上与TEM8相互作用的区域被定位到其COOH末端的C5结构域。值得注意的是,胶原蛋白α3(VI)也以与TEM8一致的模式在肿瘤内皮中优先表达。这些结果表明,TEM8/C5相互作用可能在肿瘤血管生成中发挥重要的生物学作用。