Human small cell lung cancer cells express functional VEGF receptors, VEGFR-2 and VEGFR-3

Lung Cancer. 2004 Oct;46(1):11-9. doi: 10.1016/j.lungcan.2004.03.006.

Abstract

Studies have suggested that the vascular endothelial growth factors (VEGFs)/VEGF receptors (VEGF-Rs) system plays an important role in tumour growth and metastasis. We conducted the present study to clarify whether small cell lung cancer (SCLC) cells express functional VEGF-Rs and VEGFs, and their biological significance in the SCLC progression. We examined expression of VEGF and VEGF-C, and their receptors, VEGFR-2 and VEGFR-3, in five SCLC cell lines, NCI-H82, H209, H510, H526 and H660, by Western blotting. We evaluated whether hypoxic conditions up-regulate these protein expressions. We also examined whether VEGF addition and VEGF-D addition cause phosphorylation of the mitogen-activated protein kinase (MAPK) as well as VEGFR-2 and VEGFR-3. Further, we investigated whether VEGF addition and VEGF-D addition induced the proliferation and migration of the SCLC cells. VEGF, VEGF-C, VEGFR-2 and VEGFR-3 were detectable by Western blotting in all five SCLC cell lines,. The VEGF-Rs and VEGFs expression levels were increased by an incubation under hypoxic conditions in NCI-H82. VEGF addition and VEGF-D addition caused phosphorylation of MAPK as well as the VEGF-Rs themselves, and induced proliferation and migration of the SCLC cells. These results suggested potential of VEGF signal-pathway inhibitors as anti-cancer agents in SCLC treatment disturbing growth and migration of the cancer cells.

MeSH terms

  • Blotting, Western
  • Carcinoma, Small Cell / genetics*
  • Carcinoma, Small Cell / pathology*
  • Cell Movement
  • Gene Expression Profiling*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Phosphorylation
  • Signal Transduction
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor C / biosynthesis
  • Vascular Endothelial Growth Factor Receptor-2 / biosynthesis*
  • Vascular Endothelial Growth Factor Receptor-3 / biosynthesis*

Substances

  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor C
  • Vascular Endothelial Growth Factor Receptor-2
  • Vascular Endothelial Growth Factor Receptor-3