PMID- 29249192
OWN - NLM
STAT- MEDLINE
DCOM- 20190318
LR  - 20190318
IS  - 1029-2403 (Electronic)
IS  - 1026-8022 (Linking)
VI  - 59
IP  - 9
DP  - 2018 Sep
TI  - DNA damage response-initiated cytokine secretion in bone marrow stromal cells 
      promotes chemoresistance of myeloma cells.
PG  - 2220-2226
LID - 10.1080/10428194.2017.1413188 [doi]
AB  - Acquisition of chemoresistance accounts for a major cause of chemotherapy failure 
      for multiple myeloma (MM). Bone marrow stromal cells (BMSCs) are considered to 
      play a pivotal role in modulating drug resistance of MM cells. However, the 
      underlying mechanism whereby BMSCs, particularly damaged stromal cells, affects 
      chemoresistance has not been identified yet. Here, we show exposure to 
      doxorubicin doxorubicin (Dox) induced dramatic ATM 
      (ataxia-telangiectasia-mutated)-dependent DNA damage response (DDR) and increased 
      secretion of interleukin (IL)-6 in HS-5 cell line and primary BMSCs derived from 
      healthy donors. Specifically, IL-6-containing conditioned media (CM) derived from 
      Dox-pretreated stromal cells displayed significant protective effect on 
      Dox-induced apoptosis of MM cells. Also, treatment of BMSCs with ATM kinase 
      inhibitor markedly reduced IL-6 secretion and concurrently, partially reversed 
      CM-mediated chemoresistance in myeloma cells. These data indicate that 
      DNA-damaging drug triggers an ATM-dependent DDR in BMSCs, leading to increased 
      cytokine secretion and resistance of myeloma cells to chemotherapy-induced 
      apoptosis.
FAU - Tang, Hailong
AU  - Tang H
AD  - a Department of Hematology , Xijing Hospital, Fourth Military Medical University 
      , Xi'an , Shaanxi , China.
FAU - Shu, Mimi
AU  - Shu M
AD  - a Department of Hematology , Xijing Hospital, Fourth Military Medical University 
      , Xi'an , Shaanxi , China.
FAU - Dai, Bo
AU  - Dai B
AD  - b Shaanxi Center for Stem Cell Application Engineering Research , Xi'an , Shaanxi 
      , China.
FAU - Xu, Li
AU  - Xu L
AD  - a Department of Hematology , Xijing Hospital, Fourth Military Medical University 
      , Xi'an , Shaanxi , China.
FAU - Dong, Baoxia
AU  - Dong B
AD  - a Department of Hematology , Xijing Hospital, Fourth Military Medical University 
      , Xi'an , Shaanxi , China.
FAU - Gao, Guangxun
AU  - Gao G
AD  - a Department of Hematology , Xijing Hospital, Fourth Military Medical University 
      , Xi'an , Shaanxi , China.
FAU - Chen, Xiequn
AU  - Chen X
AD  - a Department of Hematology , Xijing Hospital, Fourth Military Medical University 
      , Xi'an , Shaanxi , China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171218
PL  - United States
TA  - Leuk Lymphoma
JT  - Leukemia & lymphoma
JID - 9007422
RN  - 0 (2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one)
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Interleukin-6)
RN  - 0 (Morpholines)
RN  - 0 (Pyrones)
RN  - 80168379AG (Doxorubicin)
RN  - EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
SB  - IM
MH  - Antibiotics, Antineoplastic/pharmacology
MH  - Apoptosis/drug effects
MH  - Ataxia Telangiectasia Mutated Proteins/antagonists & inhibitors/metabolism
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - Cells, Cultured
MH  - *DNA Damage
MH  - Doxorubicin/*pharmacology
MH  - Drug Resistance, Neoplasm/*drug effects
MH  - Humans
MH  - Interleukin-6/*metabolism
MH  - Mesenchymal Stem Cells/*drug effects/metabolism
MH  - Morpholines/pharmacology
MH  - Multiple Myeloma/genetics/metabolism/pathology
MH  - Pyrones/pharmacology
OTO - NOTNLM
OT  - DNA damage response
OT  - Myeloma
OT  - bone marrow stromal cell
OT  - cytokine
OT  - doxorubicin
OT  - drug resistance
EDAT- 2017/12/19 06:00
MHDA- 2019/03/19 06:00
CRDT- 2017/12/19 06:00
PHST- 2017/12/19 06:00 [pubmed]
PHST- 2019/03/19 06:00 [medline]
PHST- 2017/12/19 06:00 [entrez]
AID - 10.1080/10428194.2017.1413188 [doi]
PST - ppublish
SO  - Leuk Lymphoma. 2018 Sep;59(9):2220-2226. doi: 10.1080/10428194.2017.1413188. Epub 
      2017 Dec 18.