Induction of multiple myeloma bone marrow stromal cell apoptosis by inhibiting extracellular vesicle miR-10a secretion

Blood Adv. 2019 Nov 12;3(21):3228-3240. doi: 10.1182/bloodadvances.2019000403.

Abstract

Bone marrow stromal cells (BMSCs) interact with multiple myeloma (MM) cells in the bone marrow and create a permissive microenvironment for MM cell proliferation and survival. In this study, we investigated the role of extracellular vesicles (EVs) from BMSCs derived from patients with MM (MM-BMSCs). EV-encapsulated miR-10a expression was high while intracellular miR-10a was low in MM-BMSCs. We therefore hypothesized that miR-10a was packaged into EVs that were actively released into the extracellular space. Inhibition of EV release resulted in accumulation of intracellular miR-10a, inhibition of cell proliferation, and induction of apoptosis in MM-BMSCs. In contrast, proliferation and apoptosis of BMSCs derived from healthy individuals were unaffected by inhibition of EV release. Furthermore, miR-10a derived from MM-BMSCs was transferred into MM cells via EVs and enhanced their proliferation. These results suggest that inhibition of EV release induced apoptosis in MM-BMSCs and inhibited MM cell proliferation, indicating a possible role for MM-BMSC-targeted therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apoptosis / genetics*
  • Biological Transport
  • Biomarkers
  • Cell Proliferation
  • Cell Survival
  • Extracellular Vesicles / metabolism*
  • Female
  • Gene Expression
  • Humans
  • Male
  • Membrane Glycoproteins / genetics*
  • Mesenchymal Stem Cells / metabolism*
  • Mesenchymal Stem Cells / pathology
  • Middle Aged
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / metabolism*
  • Neoplasm Staging
  • Receptors, Immunologic / genetics*

Substances

  • Biomarkers
  • LILRB2 protein, human
  • Membrane Glycoproteins
  • Receptors, Immunologic