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

Zhiqiang Liu, Jingda Xu, Jin He, Huan Liu, Pei Lin, Xinhai Wan, Nora M. Navone, Qiang Tong, Larry W. Kwak, Robert Z. Orlowski, Jing Yang

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

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 marrowderived adipocytes in the reduced response of myeloma cells to chemotherapy. Our findings suggest that adipocytes, adipocyte-secreted adipokines, and adipocyteactivated autophagy are novel targets for combatting chemotherapy resistance and enhancing treatment efficacy in myeloma patients.

Original languageEnglish (US)
Pages (from-to)34329-34341
Number of pages13
JournalOncotarget
Volume6
Issue number33
DOIs
StatePublished - 2015

Keywords

  • Adipocytes
  • Apoptosis
  • Autophagy
  • Chemotherapy resistance
  • Multiple myeloma

ASJC Scopus subject areas

  • Oncology

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