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An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
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An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells

Published on: July 15, 2015

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Bone marrow stromal cell-derived exosomes as communicators in drug resistance in multiple myeloma cells

Jinheng Wang1, An Hendrix2, Sophie Hernot3

  • 1Department of Hematology and Immunology, Myeloma Center Brussels, Vrije Universiteit Brussel, Brussels, Belgium; Research Center for Immunology, Xinxiang Medical University, Xinxiang, Henan, People's Republic of China;

Blood
|June 15, 2014
PubMed

Insights

Bone marrow stromal cell (BMSC)-derived exosomes promote multiple myeloma (MM) cell growth and drug resistance. These exosomes mediate communication, influencing MM cell viability, proliferation, survival, migration, and resistance to bortezomib therapy.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Bone marrow stromal cells (BMSCs) play a key role in multiple myeloma (MM) pathogenesis through secreted factors.
  • Exosomes mediate intercellular communication by transferring molecular cargo, but their specific role in BMSC-MM cell interactions is unclear.

Purpose of the Study:

  • To investigate the effect of BMSC-derived exosomes on MM cell viability, proliferation, survival, migration, and drug resistance.
  • To elucidate the role of exosome-mediated communication in the BMSC-MM cell interplay.

Main Methods:

  • Utilized the murine 5T33MM model and human MM samples.
  • Analyzed MM cell responses to BMSC-derived exosomes, including growth, drug resistance, and pathway activation.
  • Investigated exosome cargo exchange between BMSCs and MM cells.

Main Results:

  • BMSC-derived exosomes (from both naive and 5T33 models) enhanced MM cell growth and bortezomib resistance.
  • Exosomes facilitated mutual cytokine exchange between BMSCs and MM cells.
  • BMSC-derived exosomes modulated key survival pathways (JNK, p38, p53, Akt) in MM cells.
  • Exosomes from both normal and MM patient BMSCs induced survival and drug resistance in human MM cells.

Conclusions:

  • Exosome-mediated communication is involved in BMSC-induced proliferation, migration, survival, and drug resistance of MM cells.
  • BMSC-derived exosomes represent a significant factor in multiple myeloma progression and treatment resistance.

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