PMID- 31713003
OWN - NLM
STAT- MEDLINE
DCOM- 20201009
LR  - 20221207
IS  - 2211-3436 (Electronic)
IS  - 2211-3428 (Linking)
VI  - 43
IP  - 1
DP  - 2020 Feb
TI  - Exosomes derived from cancer stem cells of gemcitabine-resistant pancreatic 
      cancer cells enhance drug resistance by delivering miR-210.
PG  - 123-136
LID - 10.1007/s13402-019-00476-6 [doi]
AB  - PURPOSE: Gemcitabine (GEM)-based chemotherapy is the first-line treatment for 
      locally advanced pancreatic cancer. GEM resistance, however, remains a 
      significant clinical challenge. Here, we investigated whether exosomes derived 
      from GEM-resistant pancreatic cancer stem cells (CSCs) mediate cell-cell 
      communication between cells that are sensitive or resistant to GEM and, by doing 
      so, regulate drug resistance. METHODS: GEM-sensitive BxPC-3-derived Bx(S) and 
      PANC-1 pancreatic cancer cells were cultured with exosomes extracted from CSCs 
      isolated from GEM-resistant BxPC-3-derived Bx(R) cells (Bx(R)-CSC). The effect of 
      exosomes on drug resistance, cell cycle progression, apoptosis and miRNA 
      expression was evaluated in Bx(S) and PANC-1 cells. Relevant miRNAs associated 
      with GEM resistance were identified and the role of miR-210 in conferring drug 
      resistance was examined in vitro and in vivo. RESULTS: Bx(R)-CSC-derived exosomes 
      induced GEM resistance, inhibited GEM-induced cell cycle arrest, antagonized 
      GEM-induced apoptosis, and promoted tube formation and cell migration in Bx(S) 
      and PANC-1 cells. Elevated miR-210 expression levels were detected in Bx(R)-CSCs 
      and Bx(R)-CSC-derived exosomes compared to those in Bx(S)-CSCs and 
      Bx(S)-CSC-derived exosomes. In addition, increased expression levels of miR-210 
      were observed in Bx(S) and PANC-1 cells cultured with Bx(R)-CSC-derived exosomes 
      upon exposure to GEM in a dose-dependent manner. Also, a series of biological 
      changes was observed in Bx(S) cells after transfection with miR-210 mimics, 
      including activation of the mammalian target of rapamycin (mTOR) signaling 
      pathway, and these changes were similar to those triggered by Bx(R)-CSC-derived 
      exosomes. CONCLUSIONS: Our findings suggest that exosomes derived from 
      GEM-resistant pancreatic cancer stem cells mediate the horizontal transfer of 
      drug-resistant traits to GEM-sensitive pancreatic cancer cells by delivering 
      miR-210.
FAU - Yang, Zhiyong
AU  - Yang Z
AD  - Pancreatic Surgery Center, Department of Hepatobiliary and Pancreatic Surgery, 
      Zhongnan Hospital of Wuhan University, Wuhan, China.
FAU - Zhao, Ning
AU  - Zhao N
AD  - Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan, China.
FAU - Cui, Jing
AU  - Cui J
AD  - Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan, 430022, China.
FAU - Wu, Heshui
AU  - Wu H
AD  - Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan, 430022, China.
FAU - Xiong, Jiongxin
AU  - Xiong J
AD  - Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan, 430022, China.
FAU - Peng, Tao
AU  - Peng T
AD  - Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan, 430022, China. 
      pengtao8815@163.com.
LA  - eng
PT  - Journal Article
DEP - 20191112
PL  - Netherlands
TA  - Cell Oncol (Dordr)
JT  - Cellular oncology (Dordrecht)
JID - 101552938
RN  - 0 (Antineoplastic Agents)
RN  - 0 (MIRN210 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0W860991D6 (Deoxycytidine)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - 0 (Gemcitabine)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis/drug effects
MH  - Cell Cycle Checkpoints/drug effects
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects/genetics
MH  - Cell Survival/drug effects/genetics
MH  - Deoxycytidine/*analogs & derivatives/pharmacology
MH  - Drug Resistance, Neoplasm/*genetics
MH  - Exosomes/*drug effects/genetics/*metabolism
MH  - Gene Expression Regulation, Neoplastic/drug effects/genetics
MH  - Humans
MH  - MicroRNAs/genetics/*metabolism
MH  - Microscopy, Electron, Transmission
MH  - Neoplastic Stem Cells/cytology/*metabolism/ultrastructure
MH  - Pancreatic Neoplasms/genetics/*metabolism
MH  - Signal Transduction/drug effects/genetics
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
MH  - Gemcitabine
OTO - NOTNLM
OT  - Cancer stem cells
OT  - Drug resistance
OT  - Exosomes
OT  - Gemcitabine
OT  - MicroRNA-210
OT  - Pancreatic cancer
EDAT- 2019/11/13 06:00
MHDA- 2020/10/10 06:00
CRDT- 2019/11/13 06:00
PHST- 2019/09/17 00:00 [accepted]
PHST- 2019/11/13 06:00 [pubmed]
PHST- 2020/10/10 06:00 [medline]
PHST- 2019/11/13 06:00 [entrez]
AID - 10.1007/s13402-019-00476-6 [pii]
AID - 10.1007/s13402-019-00476-6 [doi]
PST - ppublish
SO  - Cell Oncol (Dordr). 2020 Feb;43(1):123-136. doi: 10.1007/s13402-019-00476-6. Epub 
      2019 Nov 12.