PMID- 29416638
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 9
IP  - 1
DP  - 2018 Jan 2
TI  - Nicotine-enhanced stemness and epithelial-mesenchymal transition of human 
      umbilical cord mesenchymal stem cells promote tumor formation and growth in nude 
      mice.
PG  - 591-606
LID - 10.18632/oncotarget.22712 [doi]
AB  - Cigarette smoking is a well-known risk factor in the development and progression 
      of malignant diseases. Nicotine, the major constituent in cigarette smoke, has 
      also shown negative effects on stem cells. Mesenchymal stem cells (MSCs) have 
      been widely demonstrated to migrate into tumors and play key roles in cancer 
      progression. However, the mechanisms by which nicotine impacts MSCs and 
      tumorigenesis of lung cancer are still undetermined. In this study we 
      investigated the effects of nicotine on human umbilical cord mesenchymal stem 
      cells (hUC-MSCs) and the impacts of nicotine-treated hUC-MSCs on tumor formation 
      and progression. We found that nicotine has a toxic effect on hUC-MSCs and 
      changes the morphology, inhibits proliferation and promotes apoptosis of hUC-MSCs 
      in a dose-dependent manner. Nicotine-treated hUC-MSCs produce higher level of 
      IL-6. Moreover, nicotine promotes migration, stemness and epithelial-mesenchymal 
      transition (EMT) of hUC-MSCs by inhibiting E-cadherin expression and upregulating 
      mesenchymal markers such as N-cadherin and Vimentin, leading to the induction of 
      stem cell markers Sox2, Nanog, Sall4, Oct4 and CD44. Migration and proliferation 
      of non-small cell lung cancer A549 cells and breast cancer MCF-7 cells are 
      promoted after their coculture with nicotine-treated hUC-MSCs in a cell-cell 
      contact-independent manner. Furthermore, nicotine-treated hUC-MSCs promote tumor 
      formation and growth of A549 cells in nude mice. These studies demonstrated that 
      the enhanced stemness and EMT of hUC-MSCs induced by nicotine are critical for 
      the development of tobacco-related cancers.
FAU - Li, Tao
AU  - Li T
AD  - School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.
FAU - Zhang, Jun
AU  - Zhang J
AD  - Department of Laboratory, The Affiliated Hospital of Yangzhou University, 
      Yangzhou, Jiangsu 225001, P.R. China.
FAU - Zhang, Jiahui
AU  - Zhang J
AD  - School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.
FAU - Zhang, Nannan
AU  - Zhang N
AD  - School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.
FAU - Zeng, Yang
AU  - Zeng Y
AD  - Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical 
      School, Boston, MA 02114, USA.
FAU - Tang, Shengnan
AU  - Tang S
AD  - School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.
FAU - Tao, Zehua
AU  - Tao Z
AD  - School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.
FAU - Qu, Xiying
AU  - Qu X
AD  - Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical 
      School, Boston, MA 02114, USA.
FAU - Jia, Jue
AU  - Jia J
AD  - The Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. 
      China.
FAU - Zhu, Wei
AU  - Zhu W
AD  - School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.
FAU - Sun, Xiaochun
AU  - Sun X
AD  - School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.
FAU - Chen, Huabiao
AU  - Chen H
AD  - School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212001, P.R. China.
AD  - Vaccine and Immunotherapy Center, Massachusetts General Hospital, Harvard Medical 
      School, Boston, MA 02114, USA.
LA  - eng
PT  - Journal Article
DEP - 20171127
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5787492
OTO - NOTNLM
OT  - EMT
OT  - cancer
OT  - mesenchymal stem cells
OT  - nicotine
OT  - stemness
COIS- CONFLICTS OF INTEREST The authors declare that they have no competing interests.
EDAT- 2018/02/09 06:00
MHDA- 2018/02/09 06:01
PMCR- 2018/01/02
CRDT- 2018/02/09 06:00
PHST- 2017/03/21 00:00 [received]
PHST- 2017/11/01 00:00 [accepted]
PHST- 2018/02/09 06:00 [entrez]
PHST- 2018/02/09 06:00 [pubmed]
PHST- 2018/02/09 06:01 [medline]
PHST- 2018/01/02 00:00 [pmc-release]
AID - 22712 [pii]
AID - 10.18632/oncotarget.22712 [doi]
PST - epublish
SO  - Oncotarget. 2017 Nov 27;9(1):591-606. doi: 10.18632/oncotarget.22712. eCollection 
      2018 Jan 2.