Cell-derived microvesicles mediate the delivery of miR-29a/c to suppress angiogenesis in gastric carcinoma

Cancer Lett. 2016 Jun 1;375(2):331-339. doi: 10.1016/j.canlet.2016.03.026. Epub 2016 Mar 18.

Abstract

Microvesicles (MVs) secreted from cells have been found to mediate signal transduction between cells. In the tumor microenvironment, VEGF released from cancer cells plays a key role in promoting tumor angiogenesis. In this study, we characterized the inhibitory effect of MV-delivered miR-29a/c on angiogenesis and tumor growth in gastric cancer (GC). We found that the downregulation of miR-29a/c increases VEGF expression and release in GC cells, promoting the growth of vascular cells. By simulating the tumor microenvironment, the MV-delivered miR-29a/c significantly suppresses VEGF expression in GC cells, inhibiting vascular cell growth, metastasis, and tube formation. We also used a tumor implantation mouse model to show that secreted MVs containing overexpressed miR-29a/c significantly reduced the growth rate of the vasculature and tumors in vivo. To conclude, our results contribute to a novel anti-cancer strategy using miRNA-containing MVs to control tumor cell growth by blocking angiogenesis.

Keywords: Angiogenesis; Gastric cancer; Microvesicle; VEGF; miR-29.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma / drug therapy
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cell-Derived Microparticles / genetics
  • Drug Delivery Systems
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • Neovascularization, Pathologic / genetics*
  • Neovascularization, Pathologic / therapy
  • Stomach Neoplasms / drug therapy
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • Tumor Microenvironment
  • Vascular Endothelial Growth Factor A / biosynthesis*
  • Vascular Endothelial Growth Factor A / genetics
  • Xenograft Model Antitumor Assays

Substances

  • MIRN29a microRNA, human
  • MicroRNAs
  • Vascular Endothelial Growth Factor A