About
Similarities in the patterns of branching of blood vessels and nerves during growth and development have been acknowledged for some time. Biochemical and genetic confirmation of these anatomical findings has emerged recently with the identification that similar families of proteins control both axonal guidance in the nervous system and blood vessel development as well. My work focuses on two of these proteins, Semaphorin 4D (SEMA4D) and its receptor, Plexin-B1, and their role in tumor-induced angiogenesis (TIA), perineural invasion (PNI) and other features of aggressive tumor growth.
We have observed that Plexin-B1 is highly expressed not only in nerves, but also in endothelial cells, where it promotes an angiogenic phenotype when bound by SEMA4D. Interestingly, we have shown that SEMA4D is overexpressed by the transformed cells of many different aggressive malignancies that exhibit profound TIA and PNI, characteristics correlated with an inability to arrest local spread of disease and eventual onset of metastasis. These findings suggest that the class IV semaphorins may play a role in enhanced invasive behavior, though the mechanism through which this occurs remains unknown. Currently, we are studying transcriptional control of SEMA4D, the pathways activated by Plexin-B1 and the biological relevance of these proteins in human malignancy. I believe our work will help to uncover an important mechanism of tumor cell behavior, thereby presenting new therapeutic targets in the treatment of advanced neoplasms.
