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

Oncogene volume 24, pages 2647–2653 (2005)Cite this article

Abstract

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-κB 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.

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Acknowledgements

We thank Christine Wogan from the Department of Scientific Publications and Rita Hernandez from the Department of Surgical Oncology for editorial assistance. This work was supported by the Jon and Suzie Hall Fund for Colon Cancer Research (LME), NIH T32 grant (JSW, TWB), NIH CA112390 (LME) and NIH CCSG CA16672.

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Authors and Affiliations

  1. Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Fan Fan, Jane S Wey, Anna Belcheva, Wenbiao Liu, Ray J Somcio & Lee M Ellis

  2. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Marya F McCarty, Todd W Bauer & Lee M Ellis

  3. ImClone Systems Incorporated, New York, NY, USA

    Yan Wu, Andrea Hooper & Daniel J Hicklin

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  1. Fan Fan
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Correspondence to Lee M Ellis.

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Fan, F., Wey, J., McCarty, M. et al. Expression and function of vascular endothelial growth factor receptor-1 on human colorectal cancer cells. Oncogene 24, 2647–2653 (2005). https://doi.org/10.1038/sj.onc.1208246

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