PMID- 32663573
OWN - NLM
STAT- MEDLINE
DCOM- 20200917
LR  - 20200917
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 257
DP  - 2020 Sep 15
TI  - Overexpression of heme oxygenase-1 in bone marrow stromal cells promotes multiple 
      myeloma resistance through the JAK2/STAT3 pathway.
PG  - 118088
LID - S0024-3205(20)30839-0 [pii]
LID - 10.1016/j.lfs.2020.118088 [doi]
AB  - AIMS: Bone marrow stromal cells (BMSCs) have been reported to interact with 
      multiple myeloma (MM) and exert a vital function of the survival of MM cells. 
      Heme oxygenase-1 (HO-1), a cytoprotective enzyme, has the potential to become a 
      hematological malignancies targeted gene. This study aimed to investigate the 
      role of HO-1 in MM resistance of BMSCs and its possible mechanisms. MAIN METHODS: 
      In this study, the expression of related proteins was detected by RT-qPCR and 
      Western blot. HO-1 expression was regulated by lentivirus transfection. Cell 
      viability and apoptosis were detected by Flow cytometry and CCK-8. Cytokine 
      secretion was assayed by ELISA. The survival and carcinogenic abilities was 
      detected by clone formation assay. KEY FINDINGS: HO-1 expression in the BMSCs of 
      stage III MM patients was substantially increased, compared with that of healthy 
      donors and stage I/II patients. The results of co-culture of BMSCs and MM cells 
      indicated that, the upregulated HO-1 inhibited the apoptosis of co-cultured MM 
      cells, while downregulated HO-1 promoted the chemosensitivity of co-cultured MM 
      cells, moreover, the upregulated HO-1 in BMSCs increased the colony-formation 
      ability of MM cells. This protective capability may be regulated by CXCL12/CXCR4 
      signaling. High HO-1 expression in BMSCs can promote the phosphorylation of the 
      JAK2/STAT3 pathway, thereby increasing secretion of SDF-1 in BMSCs and activating 
      CXCL12/CXCR4 signaling. In addition, direct contact between BMSCs and MM cells 
      may cause drug resistance. SIGNIFICANCE: These results indicated that the 
      regulation of HO-1 in BMSCs may be a new effective method of MM therapy.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Huang, Jun
AU  - Huang J
AD  - Department of Hematology, Yijishan Hospital, The First Affiliated Hospital of 
      Wannan Medical College, Wuhu 241001, China.
FAU - Huang, Lai-Quan
AU  - Huang LQ
AD  - Department of Hematology, Yijishan Hospital, The First Affiliated Hospital of 
      Wannan Medical College, Wuhu 241001, China.
FAU - He, He-Sheng
AU  - He HS
AD  - Department of Hematology, Yijishan Hospital, The First Affiliated Hospital of 
      Wannan Medical College, Wuhu 241001, China.
FAU - Yan, Jiawei
AU  - Yan J
AD  - Department of Hematology, Yijishan Hospital, The First Affiliated Hospital of 
      Wannan Medical College, Wuhu 241001, China.
FAU - Huang, Chen
AU  - Huang C
AD  - Department of Hematology, Yijishan Hospital, The First Affiliated Hospital of 
      Wannan Medical College, Wuhu 241001, China.
FAU - Wang, Ran
AU  - Wang R
AD  - Department of Hematology, Yijishan Hospital, The First Affiliated Hospital of 
      Wannan Medical College, Wuhu 241001, China.
FAU - Guan, Yan
AU  - Guan Y
AD  - Wannan Medical College, Wuhu 241001, China.
FAU - Huang, Dong-Ping
AU  - Huang DP
AD  - Department of Hematology, Yijishan Hospital, The First Affiliated Hospital of 
      Wannan Medical College, Wuhu 241001, China. Electronic address: hdp_9713@163.com.
LA  - eng
PT  - Journal Article
DEP - 20200712
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Antineoplastic Agents)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 2.7.10.2 (JAK2 protein, human)
RN  - EC 2.7.10.2 (Janus Kinase 2)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/genetics
MH  - Case-Control Studies
MH  - Coculture Techniques
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Heme Oxygenase-1/*genetics
MH  - Humans
MH  - Janus Kinase 2/metabolism
MH  - Male
MH  - Mesenchymal Stem Cells/*cytology
MH  - Middle Aged
MH  - Multiple Myeloma/drug therapy/genetics/*pathology
MH  - Neoplasm Staging
MH  - STAT3 Transcription Factor/metabolism
OTO - NOTNLM
OT  - Bone marrow stromal cell
OT  - CXCL12/CXCR4 axis
OT  - Drug resistance
OT  - Heme oxygenase-1
OT  - Multiple myeloma
COIS- Declaration of competing interest The authors declare that there are no conflicts 
      of interest.
EDAT- 2020/07/15 06:00
MHDA- 2020/09/18 06:00
CRDT- 2020/07/15 06:00
PHST- 2020/02/19 00:00 [received]
PHST- 2020/06/09 00:00 [revised]
PHST- 2020/07/08 00:00 [accepted]
PHST- 2020/07/15 06:00 [pubmed]
PHST- 2020/09/18 06:00 [medline]
PHST- 2020/07/15 06:00 [entrez]
AID - S0024-3205(20)30839-0 [pii]
AID - 10.1016/j.lfs.2020.118088 [doi]
PST - ppublish
SO  - Life Sci. 2020 Sep 15;257:118088. doi: 10.1016/j.lfs.2020.118088. Epub 2020 Jul 
      12.