Cell surface tumor endothelial markers are conserved in mice and humans.
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.
Carson-Walter
E B
EB
The Howard Hughes Medical Institute, Baltimore, Maryland 21231, USA.
Watkins
D N
DN
Nanda
A
A
Vogelstein
B
B
Kinzler
K W
KW
St  Croix
B
B
D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000098:blood supply; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D008546:Melanoma, Experimental / Q000098:blood supply; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins; D009389:Neovascularization, Pathologic / Q000235:genetics* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C510620:PLXDC1 protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface