Expression and function of vascular endothelial growth factor receptor-1 on human colorectal cancer cells

Oncogene. 2005 Apr 14;24(16):2647-53. doi: 10.1038/sj.onc.1208246.


Vascular endothelial growth factor (VEGF) is associated with tumor angiogenesis and poor prognosis in human colorectal cancer (CRC). VEGF receptor-1 (VEGFR-1 or Flt-1) is a high-affinity receptor for VEGF and is typically considered specific to endothelial cells. Here we report the expression and function of VEGFR-1 in CRC cell lines. VEGFR-1 was expressed in all CRC cell lines studied as determined by RT-PCR, Western blot analysis, FACS, and ELISA. Treatment of the human CRC cell lines HT-29 and SW480 with VEGF-A (a ligand for both VEGFR-1 and -2) or VEGF-B (a ligand specific for VEGFR-1) led to activation of Erk-1/2, SAPK/JNK, and translocation of the p65 subunit of nuclear factor-kappaB into the nucleus. Both VEGF-A and -B led to significant induction of cell motility and invasiveness of CRC cells. Stimulation of cells with VEGF-A or -B also led to larger and more numerous colonies in soft agar. However, activation of VEGFR-1 did not increase CRC cell proliferation. In contrast to the previous paradigm that VEGFRs are not present on tumor cells of epithelial origin, we found that VEGFR-1 is present and functional on CRC cells, and activation by VEGF family ligands can activate processes involved in tumor progression and metastasis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blotting, Western
  • Cell Movement / drug effects
  • Cell Proliferation
  • Colorectal Neoplasms / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunohistochemistry
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor Receptor-1 / biosynthesis*


  • Vascular Endothelial Growth Factor Receptor-1