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Multiple Myeloma-Derived Exosomes Regulate the Functions of Mesenchymal Stem Cells Partially via Modulating miR-21

Qian Cheng1,2, Xin Li1, Jingru Liu3

  • 1Department of Hematology, The Third Xiangya Hospital of Central South University, Changsha 40013, China.

Stem Cells International
|January 16, 2018
PubMed

Insights

Multiple myeloma (MM) exosomes promote mesenchymal stem cell (MSC) proliferation and cancer-associated fibroblast (CAF) transformation. This process involves microRNAs (miRs) miR-21 and miR-146a, influencing IL-6 secretion and MM cell survival.

Area of Science:

  • Cancer Biology
  • Stem Cell Biology
  • Molecular Biology

Background:

  • Exosomes from cancer cells influence mesenchymal stem cell (MSC) functions via microRNAs (miRs).
  • Specific miRs, like miR-21 and miR-146a, impact MSC proliferation and transformation.
  • Transformed MSCs secrete Interleukin-6 (IL-6), supporting multiple myeloma (MM) cell survival.

Purpose of the Study:

  • To investigate the effects of OPM2 (a MM cell line) exosomes (OPM2-exo) on MSC proliferation, cancer-associated fibroblast (CAF) transformation, and IL-6 secretion.
  • To determine the specific roles of miR-21 and miR-146a in these OPM2-exo-induced MSC alterations.

Main Methods:

  • Coculture of MSCs with OPM2-exo.
  • Quantification of miR-21 and miR-146a levels in OPM2-exo and MSCs.
  • Assessment of MSC proliferation, CAF markers (FAP, α-SMA, SDF-1), and IL-6 secretion.
  • Inhibition of miR-21 or miR-146a to evaluate their functional roles.

Main Results:

  • OPM2-exo contain high levels of miR-21 and miR-146a.
  • OPM2-exo significantly increased MSC proliferation and upregulated miR-21 and miR-146a.
  • OPM2-exo induced MSC CAF transformation, marked by increased FAP, α-SMA, SDF-1, and IL-6 secretion.
  • Inhibiting miR-21 or miR-146a attenuated the effects of OPM2-exo on MSCs.

Conclusions:

  • Multiple myeloma exosomes promote MSC proliferation and CAF transformation.
  • MM exosomes influence MSCs partly by regulating miR-21 and miR-146a.
  • This interaction enhances IL-6 secretion from MSCs, potentially supporting MM progression.

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