Sung Won Han Rose Hills
Defining the interaction between c-Met and beta-1 integrin in invasive resistance to anti-angiogenic therapy in glioblastoma
Glioblastoma is one of the most aggressive brain cancers. Recent studies have shown that only a subset of patients exhibit enduring response to anti-angiogenic therapy, which inhibits the growth of blood vessels, approximately half developing acquired resistance after initial response (anti-angiogenic factors include VEGF and bevacizumab). A key feature of anti-agniogenic resistance is the manifestation of a more invasive tumor, and it has been identified that tumor cell invasion is dictated by chemotaxis, cellular movement due to a soluble factor gradient, and haptotaxis, cellular movement due to molecules within the extracellular matrix. Recent work in the Aghi lab has shown that c-Met, a chemotactic factor, and beta-1 integrin, a haptotactic factor, are both up-regulated in patients with bevacizumab-resistant glioblastomas (BRGs). My project aims to examine the physical and functional interaction between c-Met and beta-1 integrin in hopes of better understanding the aggressive and invasive nature of BRGs.