Blood vessels and tumor progression: The neuropilin connection
The laboratory of Prof. Neufeld investigates molecular mechanisms that contribute to the development and progression of cancer. Specifically, the laboratory focuses on molecular mechanisms that control the growth of new blood vessels into tumors (tumor angiogenesis). Fifteen years ago we studied the major angiogenesis promoting protein, VEGF. From the single gene encoding VEGF are produced several alternatively spliced forms of VEGF. We hypothesized that there may exist receptors that will only recognize specific forms of VEGF. We have identified such receptors and they turned out to be neuropilins, receptors that were previously known to be receptors for axon guidance factors of the semaphorin family. These findings lead to the identification of some semaphorins as anti-angiogenic and anti-tumorigenic factors. The laboratory is currently focused on the study of the function of the neuropilins and of their associated plexin receptors in angiogenesis and in tumor progression. In addition, work from the laboratory also identified a member of the lysyl-oxidase gene family, Loxl2, as an enzyme that plays an important role in the regulation of tumor metastasis. We are currently investigating the molecular mechanisms used by Loxl2 to promote tumor metastasis and on the characterization of genes whose expression is up or down regulated in tumorigenic cells that over-express Loxl2.