Vascular endothelial growth factor (VEGF) is a survival factor for neuropilin-1-expressing lung tumour cells

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17084 Background: Lung cancer is the leading cause of cancer mortality in Ireland. The formation of new blood vessels, angiogenesis, is essential for tumour growth and metastasis and is induced by several angiogenic factors, including vascular endothelial growth factor (VEGF). Several studies have suggested a role of VEGF as a survival factor for endothelial and some tumour cells. We investigated the effect of VEGF on lung tumour cell survival and examined the VEGF receptor profile of these cells. Methods: A panel of lung cancer cell lines, H460, H647, A549 and SKMES1 were treated with recombinant VEGF (100 ng/ml). Tumour cell survival was assessed using the BrdU proliferation assay. Apoptosis was examined by flow cytometry using Annexin-V and PI staining. VEGF receptor profiles for Flt-1 (VEGFR-1), KDR (VEGFR-2), Neuropilin-1 (NP1) and Neuropilin-2 (NP2) were examined at the mRNA and protein level by RT-PCR and Western blotting, respectively. Tumour cell expression of the Plexin family of signalling receptors was investigated, in addition to the class III Semaphorins which have been shown to bind the Neuropilin receptors. Results: All lung cancer cells expressed NP1 with the exception of the H460 cell line. Using endothelial cells as a positive control, neither VEGFR-1 or VEGFR-2 were identified on the panel of lung cancer cell lines examined at the mRNA and protein level. A dose-response in tumour cell proliferation was observed with the addition of VEGF at 10ng and 100ng/ml. This increase in tumour cell proliferation was significant in all NP1-positive cells, with no effect on NP1-negative H460 cells. VEGF decreased apoptosis in cells expressing NP1, with no effect observed in H460 cells. Our preliminary data show that in addition to NP1, lung cancer cells also express NP2, Plexin-A1, Sema-3A and Sema-3C mRNA which are potential mediators of the NP1 signalling cascade. Conclusions: These results demonstrate that VEGF promotes survival of lung cancer cells, potentially through NP1 signalling. We are currently examining VEGF/VEGFR signalling and the downstream anti- and pro-apoptotic pathways activated in response to VEGF on lung cancer cells. Blockade/inhibition of VEGF and its receptors may offer potential as a therapeutic biological strategy in lung cancer. No significant financial relationships to disclose.