title: In NSCLC, VEGF-A response to hypoxia may differ between squamous cell and adenocarcinoma histology.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Medicine, University of Tromso, Norway. marte.eilertsen@uit.no
authors.forename: Marte
authors.initials: M
authors.lastname: Eilertsen
authors.forename: Ingvild
authors.initials: I
authors.lastname: Pettersen
authors.forename: Sigve
authors.initials: S
authors.lastname: Andersen
authors.forename: Inigo
authors.initials: I
authors.lastname: Martinez
authors.forename: Tom
authors.initials: T
authors.lastname: Donnem
authors.forename: Lill-Tove
authors.initials: LT
authors.lastname: Busund
authors.forename: Roy M
authors.initials: RM
authors.lastname: Bremnes
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D015687:Cell Hypoxia / Q000502:physiology*; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000378:metabolism*; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis
chemical_list: D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C