PMID- 26157778
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150709
LR  - 20201001
IS  - 2287-979X (Print)
IS  - 2288-0011 (Electronic)
IS  - 2287-979X (Linking)
VI  - 50
IP  - 2
DP  - 2015 Jun
TI  - Bortezomib inhibits the survival and proliferation of bone marrow stromal cells.
PG  - 87-96
LID - 10.5045/br.2015.50.2.87 [doi]
AB  - BACKGROUND: Bortezomib is widely used for the treatment of multiple myeloma. Bone 
      marrow stromal cells (BMSCs) endow myeloma cells with survival and growth 
      advantages. However, the influence of bortezomib on BMSCs is not well elucidated. 
      We examined the effects of bortezomib on the survival and growth of BMSCs in 
      vitro. METHODS: The effects of bortezomib on the survival and proliferation of 
      the BMSC MS-5 cell line and on BMSCs obtained from healthy individuals (N=4) and 
      newly diagnosed myeloma patients (N=5) were investigated in vitro. Transmembrane 
      cell migration was evaluated using the Transwell system. A short interfering RNA 
      strategy was used to knock down the expression of chemokine (CXC motif) ligand 12 
      (CXCL12) mRNA. To examine the effects of bortezomib-exposed BMSCs on the 
      migration and localization of myeloma cells, MS-5 monolayers were treated with 
      bortezomib for 24 hr, washed, and then overlaid with human RPMI8226 myeloma 
      cells. RESULTS: Bortezomib inhibited BMSC proliferation in a 
      concentration-dependent manner, and induced cellular apoptosis. Bortezomib 
      decreased CXCL12 production by BMSCs. Knockdown of CXCL12 mRNA in BMSCs revealed 
      that CXCL12 served as an autocrine growth factor. Short-term bortezomib treatment 
      of BMSC monolayers reduced the tendency of myeloma cells to locate to positions 
      under the monolayers. CONCLUSION: Bortezomib inhibits the survival and growth of 
      BMSCs via downregulation of CXCL12, which may contribute to the clinical effects 
      of this agent.
FAU - Kim, Ha-Yon
AU  - Kim HY
AD  - Department of Drug Activity, New Drug Development Center, Medical Innovation 
      Foundation, Osong, Korea.
FAU - Moon, Ji-Young
AU  - Moon JY
AD  - Department of Internal Medicine, School of Medicine, Chungnam National 
      University, Daejeon, Korea.
FAU - Ryu, Haewon
AU  - Ryu H
AD  - Department of Internal Medicine, School of Medicine, Chungnam National 
      University, Daejeon, Korea.
FAU - Choi, Yoon-Seok
AU  - Choi YS
AD  - Department of Internal Medicine, School of Medicine, Chungnam National 
      University, Daejeon, Korea.
FAU - Song, Ik-Chan
AU  - Song IC
AD  - Department of Internal Medicine, School of Medicine, Chungnam National 
      University, Daejeon, Korea.
FAU - Lee, Hyo-Jin
AU  - Lee HJ
AD  - Department of Internal Medicine, School of Medicine, Chungnam National 
      University, Daejeon, Korea.
FAU - Yun, Hwan-Jung
AU  - Yun HJ
AD  - Department of Internal Medicine, School of Medicine, Chungnam National 
      University, Daejeon, Korea.
FAU - Kim, Samyong
AU  - Kim S
AD  - Department of Internal Medicine, School of Medicine, Chungnam National 
      University, Daejeon, Korea.
FAU - Jo, Deog-Yeon
AU  - Jo DY
AD  - Department of Internal Medicine, School of Medicine, Chungnam National 
      University, Daejeon, Korea.
LA  - eng
PT  - Journal Article
DEP - 20150625
PL  - Switzerland
TA  - Blood Res
JT  - Blood research
JID - 101605247
PMC - PMC4486164
OTO - NOTNLM
OT  - Bone marrow stromal cells
OT  - Bortezomib
OT  - CXCL12
OT  - Multiple myeloma
OT  - Proliferation
OT  - Survival
COIS- Authors' Disclosures of Potential Conflicts of Interest: No potential conflicts 
      of interest relevant to this article were reported.
EDAT- 2015/07/15 06:00
MHDA- 2015/07/15 06:01
PMCR- 2015/06/01
CRDT- 2015/07/10 06:00
PHST- 2015/03/01 00:00 [received]
PHST- 2015/05/24 00:00 [revised]
PHST- 2015/05/27 00:00 [accepted]
PHST- 2015/07/10 06:00 [entrez]
PHST- 2015/07/15 06:00 [pubmed]
PHST- 2015/07/15 06:01 [medline]
PHST- 2015/06/01 00:00 [pmc-release]
AID - 10.5045/br.2015.50.2.87 [doi]
PST - ppublish
SO  - Blood Res. 2015 Jun;50(2):87-96. doi: 10.5045/br.2015.50.2.87. Epub 2015 Jun 25.