Antiangiogenic agent sunitinib induces epithelial to mesenchymal transition and accelerates motility of colorectal cancer cells

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Author(s)

    • Tomida Chisato
    • Department of Physiological Nutrition, Institute of Medical Nutrition, University of Tokushima Graduate School
    • Yamagishi Naoko
    • Department of Anatomy and Cell Biology, School of Medicine, Wakayama Medical University
    • Nagano Hikaru
    • Department of Physiological Nutrition, Institute of Medical Nutrition, University of Tokushima Graduate School
    • Uchida Takayuki
    • Department of Physiological Nutrition, Institute of Medical Nutrition, University of Tokushima Graduate School
    • Ohno Ayako
    • Department of Physiological Nutrition, Institute of Medical Nutrition, University of Tokushima Graduate School
    • Hirasaka Katsuya
    • Graduate school of Fisheries Science and Environmental Studies, Nagasaki University
    • Nikawa Takeshi
    • Department of Physiological Nutrition, Institute of Medical Nutrition, University of Tokushima Graduate School
    • Teshima-Kondo Shigetada
    • Department of Physiological Nutrition, Institute of Medical Nutrition, University of Tokushima Graduate School

Abstract

<p>Although vascular endothelial growth factor receptor (VEGF-R)-targeted antiangiogenic agents are important treatment for a number of human malignancies, there is accumulating evidence that the therapies may promote disease progression, such as invasion and metastasis. How tumors become to promote their evasiveness remains fully uncertain. One of possible mechanisms for the adaptation may be a direct effect of VEGF-R inhibitors on tumor cells expressing VEGF-R. To elucidate a direct effect of VEGF-R-targeting drug (sunitinib), we established a human colorectal cancer cell model adapted to sunitinib. The sunitinib-conditioned cells showed a significant increase in cellular motility and migration activities, compared to the vehicle-treated control cells. Consistent with the phenotype, the sunitinib-conditioned cells decreased the expression levels of E-cadherin (an epithelial marker), while significantly increased the levels of Slug and Zeb1 (mesenchymal markers). Expression profiles of VEGF-R in the sunitinib-conditioned cells showed that only neuropilin-1 (NRP1) expression was significantly increased among all VEGF-R tested. Blockade of NRP1 using its antagonist clearly repressed the migration activation in sunitinib-conditioned cells, but not in the control cells. These results suggest that inhibition of VEGF-R on colorectal cancer cells can drive the epithelial-mesenchymal transition, leading to activation of cell motility in an NRP1-dependent manner. J. Med. Invest. 64: 250-254, August, 2017</p>

Journal

  • The Journal of Medical Investigation

    The Journal of Medical Investigation 64(3.4), 250-254, 2017

    Faculty of Medicine Tokushima University

Codes

  • NII Article ID (NAID)
    130006105181
  • NII NACSIS-CAT ID (NCID)
    AA11166929
  • Text Lang
    ENG
  • Article Type
    journal article
  • ISSN
    1343-1420
  • Data Source
    IR  J-STAGE 
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