Mature adipocytes in bone marrow protect myeloma cells against chemotherapy through autophagy activation

Oncotarget. 2015 Oct 27;6(33):34329-41. doi: 10.18632/oncotarget.6020.


A major problem in patients with multiple myeloma is chemotherapy resistance, which develops in myeloma cells upon interaction with bone marrow stromal cells. However, few studies have determined the role of bone marrow adipocytes, a major component of stromal cells in the bone marrow, in myeloma chemotherapy resistance. We reveal that mature human adipocytes activate autophagy and upregulate the expression of autophagic proteins, thereby suppressing chemotherapy-induced caspase cleavage and apoptosis in myeloma cells. We found that adipocytes secreted known and novel adipokines, such as leptin and adipsin. The addition of these adipokines enhanced the expression of autophagic proteins and reduced apoptosis in myeloma cells. In vivo studies further demonstrated the importance of bone marrow-derived adipocytes in the reduced response of myeloma cells to chemotherapy. Our findings suggest that adipocytes, adipocyte-secreted adipokines, and adipocyte-activated autophagy are novel targets for combatting chemotherapy resistance and enhancing treatment efficacy in myeloma patients.

Keywords: adipocytes; apoptosis; autophagy; chemotherapy resistance; multiple myeloma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism*
  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Blotting, Western
  • Bone Marrow Cells / metabolism
  • Cell Line, Tumor
  • Coculture Techniques
  • Drug Resistance, Neoplasm / physiology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Mice
  • Mice, SCID
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / pathology
  • Real-Time Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents