Macrophages are an abundant component of myeloma microenvironment and protect myeloma cells from chemotherapy drug-induced apoptosis.
Multiple myeloma remains an incurable disease. One of the major problems is that myeloma cells develop drug resistance on interaction with bone marrow stromal cells. In this study, we examined the effects of macrophages (Mvarphis), a type of stromal cells, on myeloma cell survival and response to chemotherapy. We showed that Mvarphi, in particular tumor-associated Mvarphi, is a protector of myeloma cells. The protective effect was dependent on direct contact between Mvarphis and myeloma cells. Mvarphis protected both myeloma cell lines and primary myeloma cells from spontaneous and chemotherapy drug-induced apoptosis by attenuating the activation and cleavage of caspase-dependent apoptotic signaling. These findings are clinically relevant because we found that CD68+ Mvarphis heavily infiltrate the bone marrow of patients with myeloma but not the bone marrow of control patients. Thus, our results indicate that Mvarphis may contribute to myeloma cell survival and resistance to chemotherapeutic treatment in vivo.
Zheng
Yuhuan
Y
Department of Lymphoma and Myeloma, Division of Cancer Medicine, Center for Cancer Immunology Research, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Cai
Zhen
Z
Wang
Siqing
S
Zhang
Xiang
X
Qian
Jianfei
J
Hong
Sungyoul
S
Li
Haiyan
H
Wang
Michael
M
Yang
Jing
J
Yi
Qing
Q
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D045744:Cell Line, Tumor / Q000378:metabolism; D002470:Cell Survival; D003907:Dexamethasone / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D008264:Macrophages / Q000502:physiology*; D008558:Melphalan / Q000494:pharmacology; D009101:Multiple Myeloma / Q000473:pathology*; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism; D000097382:CD68 Molecule
D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018906:Antineoplastic Agents, Alkylating; D003907:Dexamethasone; D008558:Melphalan; C067980:CD68 antigen, human; D000097382:CD68 Molecule