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Article

Interruption of the HGF paracrine loop by NK4, an HGF antagonist, reduces VEGF expression of CT26 cells

  • Authors:
    • Takeshi Kubota
    • Atsushi Matsumura
    • Hiroaki Taiyoh
    • Yasuhito  Izumiya
    • Hitoshi  Fujiwara
    • Kazuma Okamoto
    • Daisuke Ichikawa
    • Atsushi  Shiozaki
    • Shuhei Komatsu
    • Masayoshi Nakanishi
    • Yoshiaki Kuriu
    • Yasutoshi  Murayama
    • Hisashi Ikoma
    • Toshiya Ochiai
    • Takahiro Nakamura
    • Kunio Matsumoto
    • Toshikazu Nakamura
    • Eigo Otsuji
  • View Affiliations / Copyright

    Affiliations: Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan, Division of Tumor Dynamics and Regulation, Kanazawa University Cancer Research Institute, Ishikawa, Japan, Kringle Pharma Joint Research Division for Regenerative Drug Discovery, Center for Advanced Science and Innovation, Osaka University, Osaka, Japan
  • Pages: 567-572
    |
    Published online on: May 29, 2013
       https://doi.org/10.3892/or.2013.2509
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Abstract

Hepatocyte growth factor (HGF), acting through the c‑Met receptor, plays an important role in solid tumors. Various malignant cells utilize the biological actions of the HGF/c‑Met pathway for their dissociative, invasive and metastatic behaviors. HGF also binds to the receptor expressed on endothelial cells that stimulates angiogenesis, a process critical to continued growth of solid tumors. It is known that HGF induces in vitro expression of vascular endothelial growth factor (VEGF), a key agonist of tumor angiogenesis. In the present study, we showed using in vitro co-culture system with fibroblasts that VEGF expression of CT26 cells was amplified through tumor-stromal interaction, i.e., the HGF paracrine loop. This action was inhibited by interruption of the HGF paracrine loop by gene transfer of NK4, an HGF antagonist. In in vivo experiments, CT26 tumor growth and angiogenesis were markedly enhanced by fibroblast co-inoculation, while the effect of fibroblasts was not observed in NK4‑expressing CT26 cells. These findings suggest that NK4 exerted potent anti‑angiogenic action via indirectly inhibiting VEGF expression of tumor cells in addition to direct effects on endothelial cells. Thus, the HGF/c‑Met pathway may be a considerable candidate for molecular targeting strategy against tumor angiogenesis.
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Copy and paste a formatted citation
Spandidos Publications style
Kubota T, Matsumura A, Taiyoh H, Izumiya Y, Fujiwara H, Okamoto K, Ichikawa D, Shiozaki A, Komatsu S, Nakanishi M, Nakanishi M, et al: Interruption of the HGF paracrine loop by NK4, an HGF antagonist, reduces VEGF expression of CT26 cells. Oncol Rep 30: 567-572, 2013.
APA
Kubota, T., Matsumura, A., Taiyoh, H., Izumiya, Y., Fujiwara, H., Okamoto, K. ... Otsuji, E. (2013). Interruption of the HGF paracrine loop by NK4, an HGF antagonist, reduces VEGF expression of CT26 cells. Oncology Reports, 30, 567-572. https://doi.org/10.3892/or.2013.2509
MLA
Kubota, T., Matsumura, A., Taiyoh, H., Izumiya, Y., Fujiwara, H., Okamoto, K., Ichikawa, D., Shiozaki, A., Komatsu, S., Nakanishi, M., Kuriu, Y., Murayama, Y., Ikoma, H., Ochiai, T., Nakamura, T., Matsumoto, K., Nakamura, T., Otsuji, E."Interruption of the HGF paracrine loop by NK4, an HGF antagonist, reduces VEGF expression of CT26 cells". Oncology Reports 30.2 (2013): 567-572.
Chicago
Kubota, T., Matsumura, A., Taiyoh, H., Izumiya, Y., Fujiwara, H., Okamoto, K., Ichikawa, D., Shiozaki, A., Komatsu, S., Nakanishi, M., Kuriu, Y., Murayama, Y., Ikoma, H., Ochiai, T., Nakamura, T., Matsumoto, K., Nakamura, T., Otsuji, E."Interruption of the HGF paracrine loop by NK4, an HGF antagonist, reduces VEGF expression of CT26 cells". Oncology Reports 30, no. 2 (2013): 567-572. https://doi.org/10.3892/or.2013.2509
Copy and paste a formatted citation
x
Spandidos Publications style
Kubota T, Matsumura A, Taiyoh H, Izumiya Y, Fujiwara H, Okamoto K, Ichikawa D, Shiozaki A, Komatsu S, Nakanishi M, Nakanishi M, et al: Interruption of the HGF paracrine loop by NK4, an HGF antagonist, reduces VEGF expression of CT26 cells. Oncol Rep 30: 567-572, 2013.
APA
Kubota, T., Matsumura, A., Taiyoh, H., Izumiya, Y., Fujiwara, H., Okamoto, K. ... Otsuji, E. (2013). Interruption of the HGF paracrine loop by NK4, an HGF antagonist, reduces VEGF expression of CT26 cells. Oncology Reports, 30, 567-572. https://doi.org/10.3892/or.2013.2509
MLA
Kubota, T., Matsumura, A., Taiyoh, H., Izumiya, Y., Fujiwara, H., Okamoto, K., Ichikawa, D., Shiozaki, A., Komatsu, S., Nakanishi, M., Kuriu, Y., Murayama, Y., Ikoma, H., Ochiai, T., Nakamura, T., Matsumoto, K., Nakamura, T., Otsuji, E."Interruption of the HGF paracrine loop by NK4, an HGF antagonist, reduces VEGF expression of CT26 cells". Oncology Reports 30.2 (2013): 567-572.
Chicago
Kubota, T., Matsumura, A., Taiyoh, H., Izumiya, Y., Fujiwara, H., Okamoto, K., Ichikawa, D., Shiozaki, A., Komatsu, S., Nakanishi, M., Kuriu, Y., Murayama, Y., Ikoma, H., Ochiai, T., Nakamura, T., Matsumoto, K., Nakamura, T., Otsuji, E."Interruption of the HGF paracrine loop by NK4, an HGF antagonist, reduces VEGF expression of CT26 cells". Oncology Reports 30, no. 2 (2013): 567-572. https://doi.org/10.3892/or.2013.2509
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