In NSCLC, VEGF-A Response to Hypoxia May Differ between Squamous Cell and Adenocarcinoma Histology

Aim: To investigate if hypoxia induces vascular endothelial growth factor (VEGF)-A and VEGF-C secretion in non-small cell lung cancer (NSCLC) cells and if the secretion is cell type-dependent. Materials and Methods: Adenocarcinoma (AC) (H522, PAC) and squamous cell carcinoma (SCC) (H520) cell lines were exposed to hypoxia and normoxia. Supernatants were analysed with enzyme- linked immunosorbent assay (ELISA). Tissue microarrays, from 304 patients diagnosed with stage I-IIIA NSCLC, were immunohistochemically-stained and scored for VEGF-A and VEGF-C. Results: In vitro, VEGF-A expression in hypoxic AC cells was significantly higher than that in normoxic cells (H522: p=0.004, PAC; p=0.007). In contrast, hypoxia led to significantly reduced VEGF-A production in the SCC cell line compared to normoxic cells (p=0.005). Conclusion: In vitro, AC and SCC exhibit different VEGF-A responses to hypoxia. Hypoxia mediates a pro-angiogenic response in AC, but apparently not in SCC. Lung cancer is the leading cause of cancer death in the