Sialyllactose suppresses angiogenesis by inhibiting VEGFR-2 activation, and tumor progression

Tae Wook Chung, Eun Young Kim, Seok Jo Kim, Hee Jung Choi, Se Bok Jang, Keuk Jun Kim, Sun Hyung Ha, Fukushi Abekura, Choong Hwan Kwak, Cheorl Ho Kim*, Ki Tae Ha

*Corresponding author for this work

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

The oligosaccharides in human milk have various biological functions. However, the molecular mechanism(s) underlying the anti-angiogenic action of sialylated human milk oligosaccharides (HMOs) are still unclear. Here, we show that siallylactose (SL) found in human milk can inhibit the activation of vascular endothelial growth factor (VEGF)- mediated VEGF receptor-2 (VEGFR-2) by binding to its VEGF binding site (second and third IgG-like domains), thus blocking downstream signal activation. SL also inhibits growth of VEGF-stimulated endothelial cells. In endothelial cells treated with VEGF, SL diminished tube formation, migration, and the arrangement of actin filament. In addition, SL clearly suppressed VEGF-induced neovascularization in an in vivo Matrigel plug assay. Notably, SL prevented the growth of tumor cells, and angiogenesis on tumor tissues in in vivo mice models allotransplanted with Lewis lung carcinoma, melanoma, and colon carcinoma cells. Taken together, we have demonstrated that the sialylated milk oligosaccharide sialyllactose functions as an inhibitor of angiogenesis through suppression of VEGFmediated VEGFR-2 activation in endothelial cells, Accordingly, it could be a novel candidate for the development of anti-angiogenic drugs without any side effects.

Original languageEnglish (US)
Pages (from-to)58152-58162
Number of pages11
JournalOncotarget
Volume8
Issue number35
DOIs
StatePublished - Jan 1 2017

Keywords

  • Angiogenesis
  • Milk
  • Oligosaccharides
  • Sialyllactose
  • VEGF receptor-2

ASJC Scopus subject areas

  • Oncology

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    Chung, T. W., Kim, E. Y., Kim, S. J., Choi, H. J., Jang, S. B., Kim, K. J., Ha, S. H., Abekura, F., Kwak, C. H., Kim, C. H., & Ha, K. T. (2017). Sialyllactose suppresses angiogenesis by inhibiting VEGFR-2 activation, and tumor progression. Oncotarget, 8(35), 58152-58162. https://doi.org/10.18632/oncotarget.16192