Cell surface tumor endothelial markers are conserved in mice and humans.
Cell surface tumor endothelial markers are conserved in mice and humans.
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发表时间：
2001-09
期刊：
影响因子：
11.2
通讯作者：
E. Carson-Walter;D. N. Watkins;D. N. Watkins;A. Nanda;B. Vogelstein;K. Kinzler;B. S. Croix
中科院分区：
文献类型：
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作者：
E. Carson-Walter;D. N. Watkins;D. N. Watkins;A. Nanda;B. Vogelstein;K. Kinzler;B. S. Croix
我们最近发现了编码肿瘤内皮标志物(TEM)的基因，这些基因在肿瘤血管生成过程中表现出高表达。从生物学和临床的角度来看，与细胞表面膜相关的TEM尤其令人感兴趣。因此，我们进一步鉴定了四个这样的基因，TEM1，TEM5，TEM7和TEM8，它们都含有可能的跨膜结构域。TEM5似乎是一种七次跨膜受体，而TEM1、TEM7和TEM8只跨越一次膜。我们确定了这些基因中每一个的小鼠对应物，分别命名为mTEM1、mTEM5、mTEM7和mTEM8。对小鼠肿瘤、胚胎和成人组织中这些mTEM的检测表明，其中三个mTEM1、mTEM5和mTEM8在肿瘤血管和发育中的胚胎的血管中大量表达。重要的是，这些mTEM在正常成年小鼠组织中的表达要么是检测不到的，要么是只在一小部分血管中检测到的。这些结果证明了人类和小鼠肿瘤血管生成在分子水平上的保守性，并支持肿瘤血管生成在很大程度上反映了正常的生理新生血管的观点。TEM1、TEM5和TEM8在人和小鼠肿瘤内皮细胞上的协同表达使这些基因成为抗血管生成治疗的靶点。
We recently identified genes encoding tumor endothelial markers (TEMs) that displayed elevated expression during tumor angiogenesis. From both biological and clinical points of view, TEMs associated with the cell surface membrane are of particular interest. Accordingly, we have further characterized four such genes, TEM1, TEM5, TEM7, and TEM8, all of which contain putative transmembrane domains. TEM5 appears to be a seven-pass transmembrane receptor, whereas TEM1, TEM7, and TEM8 span the membrane once. We identified mouse counterparts of each of these genes, designated mTEM1, mTEM5, mTEM7, and mTEM8. Examination of these mTEMs in mouse tumors, embryos, and adult tissues demonstrated that three of them (mTEM1, mTEM5, and mTEM8) were abundantly expressed in tumor vessels as well as in the vasculature of the developing embryo. Importantly, expression of these mTEMs in normal adult mouse tissues was either undetectable or detected only in a small fraction of the vessels. These results demonstrate conservation of human and mouse tumor angiogenesis at the molecular level and support the idea that tumor angiogenesis largely reflects normal physiological neovasculaturization. The coordinate expression of TEM1, TEM5, and TEM8 on tumor endothelium in humans and mice makes these genes attractive targets for the development of antiangiogenic therapies.