Human adipose mesenchymal stem cell-derived exosomal-miRNAs are critical factors for inducing anti-proliferation signalling to A2780 and SKOV-3 ovarian cancer cells

Sci Rep. 2016 Dec 8;6:38498. doi: 10.1038/srep38498.

Abstract

An enigmatic question exists concerning the pro- or anti-cancer status of mesenchymal stem cells (MSCs). Despite growing interest, this question remains unanswered, and the debate became intensified with new evidences backing each side. Here, we showed that human adipose MSC (hAMSC)-derived conditioned medium (CM) exhibited inhibitory effects on A2780 human ovarian cancer cells by blocking the cell cycle, and activating mitochondria-mediated apoptosis signalling. Explicitly, we demonstrated that exosomes, an important biological component of hAMSC-CM, could restrain proliferation, wound-repair and colony formation ability of A2780 and SKOV-3 cancer cells. Furthermore, hAMSC-CM-derived exosomes induced apoptosis signalling by upregulating different pro-apoptotic signalling molecules, such as BAX, CASP9, and CASP3, as well as downregulating the anti-apoptotic protein BCL2. More specifically, cancer cells exhibited reduced viability following fresh or protease-digested exosome treatment; however, treatment with RNase-digested exosomes could not inhibit the proliferation of cancer cells. Additionally, sequencing of exosomal RNAs revealed a rich population of microRNAs (miRNAs), which exhibit anti-cancer activities by targeting different molecules associated with cancer survival. Our findings indicated that exosomal miRNAs are important players involved in the inhibitory influence of hAMSC-CM towards ovarian cancer cells. Therefore, we believe that these comprehensive results will provide advances concerning ovarian cancer research and treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival / drug effects
  • Culture Media, Conditioned
  • Exosomes / metabolism*
  • Exosomes / ultrastructure
  • Female
  • Gene Library
  • Gene Ontology
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • MicroRNAs / metabolism*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology*
  • Reproducibility of Results
  • Signal Transduction*
  • Time Factors
  • Up-Regulation / drug effects
  • Wound Healing / drug effects

Substances

  • Culture Media, Conditioned
  • MicroRNAs