title: Mature adipocytes in bone marrow protect myeloma cells against chemotherapy through autophagy activation.
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 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.
authors.affiliation: Department of Lymphoma and Myeloma, Division of Cancer Medicine, Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Lymphoma and Myeloma, Division of Cancer Medicine, Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Jingda
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Lymphoma and Myeloma, Division of Cancer Medicine, Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Lymphoma and Myeloma, Division of Cancer Medicine, Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Pei
authors.initials: P
authors.lastname: Lin
authors.affiliation: Department of Genitourinary Medical Oncology-Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Xinhai
authors.initials: X
authors.lastname: Wan
authors.affiliation: Department of Genitourinary Medical Oncology-Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Nora M
authors.initials: NM
authors.lastname: Navone
authors.affiliation: Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Tong
authors.affiliation: Department of Lymphoma and Myeloma, Division of Cancer Medicine, Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Larry W
authors.initials: LW
authors.lastname: Kwak
authors.affiliation: Department of Lymphoma and Myeloma, Division of Cancer Medicine, Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.affiliation: Department of Lymphoma and Myeloma, Division of Cancer Medicine, Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents
keywords: adipocytes; apoptosis; autophagy; chemotherapy resistance; multiple myeloma