Expression and function of vascular endothelial growth factor receptor-1 on human colorectal cancer cells.
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.
Fan
Fan
F
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030-4009, USA.
Wey
Jane S
JS
McCarty
Marya F
MF
Belcheva
Anna
A
Liu
Wenbiao
W
Bauer
Todd W
TW
Somcio
Ray J
RJ
Wu
Yan
Y
Hooper
Andrea
A
Hicklin
Daniel J
DJ
Ellis
Lee M
LM
D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis*
D040281:Vascular Endothelial Growth Factor Receptor-1