The candidate guidance molecule, Semaphorin 5B, is over-expressed in kidney cancers

1523 Semaphorins are a family of secreted and transmembrane proteins with roles in axonal guidance, vasculogenesis, and cellular immunity. Recently, members of this family have been implicated in human cancers. Expression of the transmembrane semaphorin, Sema5B, is elevated in various kidney cancers, including clear cell carcinoma and renal adenocarcinoma; expression is low in all normal adult tissues examined. The predicted extracellular domain of Sema5B comprises sema and PSI domains and a series of juxtamembrane thrombospondin type I repeats. We have found that the expression of Sema5B is regulated by oxygen tension and is enhanced by loss of function of pVHL (the von Hippel Lindau protein), a common feature of renal cancers. Additionally, the expression of Sema5B in renal cell carcinomas correlates strongly with the expression of vascular endothelial growth factor (VEGF), a protein known to be up-regulated by hypoxia and a key mediator of angiogenesis in malignancy. The mouse putative ortholog, SemaG, is expressed through embryonic day 12 in a broad mesodermal and ectodermal pattern, consistent with a role in vasculogenesis during development; expression in the brain is also observed, as previously reported. Together, these data suggest an angiogenic and/or migratory function of Sema5B in renal cancer.