Validating the effect of anti-angiogenic treatment on tumor cell invasion and metastasis in NSCLC

• Applicant: Professor Dr. Roland Tillmann Ullrich
• Subject Area: Hematology, Oncology
• Term: from 2014 to 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 256380049

The molecular mechanisms controlling tumor angiogenesis remain poorly defined. Recently, we combined a chemical genetics approach with multimodal imaging and identified an autocrine feed-forward loop in tumor cells wherein tumor-derived VEGF stimulates VEGF production via VEGFR2-dependent activation of mTOR, providing a several-fold amplification of the initial pro-angiogenic signal (Chatterjee et al., 2013). Tumors with tumor cell specific knockdown of VEGFR2 remained very small in size and were characterized by a non-angiogenic but very invasive phenotype. It was recently found that anti-angiogenic therapy targeting VEGF augments tumor cell invasion (Paez-Ribes et al., 2009). We hypothesize that the induction of tumor cell invasion is due to anti-VEGF mediated inhibition of VEGFR2 signaling in NSCLC cells. Indeed, using a spheroid invasion model we found that drug-induced inhibition of VEGFR2 on tumor cells drives tumor cell migration. We now seek to further elucidate the molecular mechanisms how VEGF / VEGFR2 -signaling is related to tumor cell invasion. By exploiting the signaling mechanisms that induce tumor cell migration (e.g. AKT) we aim to identify therapeutically tractable targets to prevent tumor cell migration

• DFG Programme: Research Grants