PMID- 31698453
OWN - NLM
STAT- MEDLINE
DCOM- 20200901
LR  - 20200901
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 3
IP  - 21
DP  - 2019 Nov 12
TI  - Induction of multiple myeloma bone marrow stromal cell apoptosis by inhibiting 
      extracellular vesicle miR-10a secretion.
PG  - 3228-3240
LID - 10.1182/bloodadvances.2019000403 [doi]
AB  - Bone marrow stromal cells (BMSCs) interact with multiple myeloma (MM) cells in 
      the bone marrow and create a permissive microenvironment for MM cell 
      proliferation and survival. In this study, we investigated the role of 
      extracellular vesicles (EVs) from BMSCs derived from patients with MM (MM-BMSCs). 
      EV-encapsulated miR-10a expression was high while intracellular miR-10a was low 
      in MM-BMSCs. We therefore hypothesized that miR-10a was packaged into EVs that 
      were actively released into the extracellular space. Inhibition of EV release 
      resulted in accumulation of intracellular miR-10a, inhibition of cell 
      proliferation, and induction of apoptosis in MM-BMSCs. In contrast, proliferation 
      and apoptosis of BMSCs derived from healthy individuals were unaffected by 
      inhibition of EV release. Furthermore, miR-10a derived from MM-BMSCs was 
      transferred into MM cells via EVs and enhanced their proliferation. These results 
      suggest that inhibition of EV release induced apoptosis in MM-BMSCs and inhibited 
      MM cell proliferation, indicating a possible role for MM-BMSC-targeted therapy.
CI  - (c) 2019 by The American Society of Hematology.
FAU - Umezu, Tomohiro
AU  - Umezu T
AD  - Department of Hematology.
AD  - Department of Advanced Cellular Therapy, and.
FAU - Imanishi, Satoshi
AU  - Imanishi S
AD  - Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
FAU - Yoshizawa, Seiichiro
AU  - Yoshizawa S
AD  - Department of Hematology.
FAU - Kawana, Chiaki
AU  - Kawana C
AD  - Department of Hematology.
FAU - Ohyashiki, Junko H
AU  - Ohyashiki JH
AD  - Department of Advanced Cellular Therapy, and.
FAU - Ohyashiki, Kazuma
AU  - Ohyashiki K
AD  - Department of Hematology.
AD  - Department of Advanced Cellular Therapy, and.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
RN  - 0 (Biomarkers)
RN  - 0 (LILRB2 protein, human)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Receptors, Immunologic)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Apoptosis/*genetics
MH  - Biological Transport
MH  - Biomarkers
MH  - Cell Proliferation
MH  - Cell Survival
MH  - Extracellular Vesicles/*metabolism
MH  - Female
MH  - Gene Expression
MH  - Humans
MH  - Male
MH  - Membrane Glycoproteins/*genetics
MH  - Mesenchymal Stem Cells/*metabolism/pathology
MH  - Middle Aged
MH  - Multiple Myeloma/diagnosis/*genetics/*metabolism
MH  - Neoplasm Staging
MH  - Receptors, Immunologic/*genetics
PMC - PMC6855114
COIS- Conflict-of-interest disclosure: K.O. received research support from Celgene KK, 
      Chugai Pharmaceutical KK, and Janssen Pharma KK. The remaining authors declare no 
      competing financial interests.
EDAT- 2019/11/08 06:00
MHDA- 2020/09/02 06:00
PMCR- 2019/10/29
CRDT- 2019/11/08 06:00
PHST- 2019/05/07 00:00 [received]
PHST- 2019/09/22 00:00 [accepted]
PHST- 2019/11/08 06:00 [entrez]
PHST- 2019/11/08 06:00 [pubmed]
PHST- 2020/09/02 06:00 [medline]
PHST- 2019/10/29 00:00 [pmc-release]
AID - 422648 [pii]
AID - 2019/ADV2019000403 [pii]
AID - 10.1182/bloodadvances.2019000403 [doi]
PST - ppublish
SO  - Blood Adv. 2019 Nov 12;3(21):3228-3240. doi: 10.1182/bloodadvances.2019000403.