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

• Published in: Anticancer research 2012-11, Vol.32 (11), p.4729-4736
• Main Authors: EILERTSEN, Marte, PETTERSEN, Ingvild, ANDERSEN, Sigve, MARTINEZ, Inigo, DONNEM, Tom, BUSUND, Lill-Tove, BREMNES, Roy M
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - metabolism; Adenocarcinoma - pathology; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell Hypoxia - physiology; Cell Line, Tumor; Enzyme-Linked Immunosorbent Assay; Humans; Immunohistochemistry; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Medical sciences; Pneumology; Tissue Array Analysis; Tumors; Tumors of the respiratory system and mediastinum; Vascular Endothelial Growth Factor A - biosynthesis; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor C - biosynthesis
• ISSN: 0250-7005; 1791-7530

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. 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. 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). 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.