Nogo-B promotes tumor angiogenesis and provides a potential therapeutic target in hepatocellular carcinoma

Mol Oncol. 2018 Dec;12(12):2042-2054. doi: 10.1002/1878-0261.12358. Epub 2018 Oct 26.

Abstract

Tumor angiogenesis is one of the hallmarks of cancer as well as an attractive target for cancer therapy. Characterization of novel pathways that act in parallel with the VEGF/VEGFR axis to promote tumor angiogenesis may provide insights into novel anti-angiogenic therapeutic targets. We found that the expression level of Nogo-B is positively correlated with tumor vessel density in hepatocellular carcinoma (HCC). While Nogo-B depletion inhibited tumor angiogenesis, Nogo-B overexpression promoted tumor angiogenesis in a tumor xenograft subcutaneous model of the human HCC cell line. Mechanically, Nogo-B regulates tumor angiogenesis based on its association with integrin αv β3 and activation of focal adhesion kinase. Moreover, Nogo-B antibody successfully abolished the function of Nogo-B in tumor angiogenesis in vitro and in vivo. Collectively, our results strongly suggest that Nogo-B is an important tumor angiogenic factor and blocking Nogo-B selectively inhibits tumor angiogenesis.

Keywords: Nogo-B; blocking antibody; hepatocellular carcinoma; integrin; tumor angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / blood supply*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Adhesion
  • Cell Line, Tumor
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Liver Neoplasms / blood supply*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Mice, Inbred C57BL
  • Mice, Nude
  • Molecular Targeted Therapy
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology*
  • Nogo Proteins / analysis
  • Nogo Proteins / antagonists & inhibitors
  • Nogo Proteins / genetics
  • Nogo Proteins / metabolism*

Substances

  • Nogo Proteins