PMID- 26733169
OWN - NLM
STAT- MEDLINE
DCOM- 20170209
LR  - 20181202
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 37
IP  - 6
DP  - 2016 Jun
TI  - Human umbilical cord mesenchymal stem cells delivering sTRAIL home to lung cancer 
      mediated by MCP-1/CCR2 axis and exhibit antitumor effects.
PG  - 8425-35
LID - 10.1007/s13277-015-4746-7 [doi]
AB  - Mesenchymal stem cells (MSCs) are believed to be a potential vehicle delivering 
      antitumor agents for their tumor-homing capacity, while the underlying mechanism 
      is yet to be explored. The apoptotic ligand TNF-related apoptosis-inducing ligand 
      (TRAIL) has been suggested as a promising candidate for cancer gene therapy owing 
      to its advantage of selectively inducing apoptosis in cancer cells while sparing 
      normal cells. An isoleucine zipper (ISZ) added to the N-terminal of secretable 
      soluble TRAIL (sTRAIL) can generate the trimeric form of TRAIL (ISZ-sTRAIL) and 
      increase its antitumor potential. However, the inefficient delivery and toxicity 
      are still obstacles for its use. In this study, the migration of human umbilical 
      cord mesenchymal stem cells (HUMSCs) to lung cancer was observed through 
      transwell migration assay and animal bioluminescent imaging both in vitro and in 
      vivo. We found that the homing ability of HUMSCs was suppressed after either 
      knocking down the expression of monocyte chemoattractant protein-1(MCP-1) in lung 
      cancer cells or blocking CCR2 expressed on the surface of HUMSCs, indicating the 
      important role of MCP-1/CCR2 axis in the tropism of HUMSCs to lung cancer. 
      Furthermore, we genetically modified HUMSCs to deliver ISZ-sTRAIL to tumor sites 
      specifically. This targeted therapeutic system exhibited promising apoptotic 
      induction and antitumor potential in a xenograft mouse model without obvious side 
      effects. In conclusion, HUMSCs expressing ISZ-sTRAIL might be an efficient 
      therapeutic approach against lung cancer and MCP-1/CCR2 axis is essential for the 
      tumor tropism of HUMSCs.
FAU - Yan, Cihui
AU  - Yan C
AD  - Department of Immunology, Tianjin Medical University Cancer Institute and 
      Hospital; National Clinical Research Center of Cancer; Key Laboratory of Cancer 
      Immunology and Biotherapy, Tianjin, 300060, China.
FAU - Song, Xinmiao
AU  - Song X
AD  - Department of Immunology, Tianjin Medical University Cancer Institute and 
      Hospital; National Clinical Research Center of Cancer; Key Laboratory of Cancer 
      Immunology and Biotherapy, Tianjin, 300060, China.
FAU - Yu, Wenwen
AU  - Yu W
AD  - Department of Immunology, Tianjin Medical University Cancer Institute and 
      Hospital; National Clinical Research Center of Cancer; Key Laboratory of Cancer 
      Immunology and Biotherapy, Tianjin, 300060, China.
FAU - Wei, Feng
AU  - Wei F
AD  - Department of Immunology, Tianjin Medical University Cancer Institute and 
      Hospital; National Clinical Research Center of Cancer; Key Laboratory of Cancer 
      Immunology and Biotherapy, Tianjin, 300060, China.
FAU - Li, Hui
AU  - Li H
AD  - Department of Immunology, Tianjin Medical University Cancer Institute and 
      Hospital; National Clinical Research Center of Cancer; Key Laboratory of Cancer 
      Immunology and Biotherapy, Tianjin, 300060, China.
FAU - Lv, Mengguo
AU  - Lv M
AD  - Department of Immunology, Tianjin Medical University Cancer Institute and 
      Hospital; National Clinical Research Center of Cancer; Key Laboratory of Cancer 
      Immunology and Biotherapy, Tianjin, 300060, China.
FAU - Zhang, Xinwei
AU  - Zhang X
AD  - Department of Immunology, Tianjin Medical University Cancer Institute and 
      Hospital; National Clinical Research Center of Cancer; Key Laboratory of Cancer 
      Immunology and Biotherapy, Tianjin, 300060, China. zhangxinwei@tjmuch.com.
AD  - Department of Biotherapy, Tianjin Medical University Cancer Institute and 
      Hospital, Tianjin, 300060, China. zhangxinwei@tjmuch.com.
FAU - Ren, Xiubao
AU  - Ren X
AD  - Department of Immunology, Tianjin Medical University Cancer Institute and 
      Hospital; National Clinical Research Center of Cancer; Key Laboratory of Cancer 
      Immunology and Biotherapy, Tianjin, 300060, China. renxiubao@tjmuch.com.
AD  - Department of Biotherapy, Tianjin Medical University Cancer Institute and 
      Hospital, Tianjin, 300060, China. renxiubao@tjmuch.com.
LA  - eng
PT  - Journal Article
DEP - 20160105
PL  - Netherlands
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental 
      Biology and Medicine
JID - 8409922
RN  - 0 (CCL2 protein, human)
RN  - 0 (CCR2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Receptors, CCR2)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Line, Tumor
MH  - Cell Migration Assays
MH  - Cell Movement/physiology
MH  - Chemokine CCL2/*genetics/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/genetics/metabolism
MH  - Mesenchymal Stem Cells/*metabolism
MH  - Mice
MH  - Molecular Targeted Therapy
MH  - Real-Time Polymerase Chain Reaction
MH  - Receptors, CCR2/*genetics/metabolism
MH  - TNF-Related Apoptosis-Inducing Ligand/*pharmacology
MH  - Umbilical Cord/cytology
OTO - NOTNLM
OT  - CCR2
OT  - Lung cancer
OT  - MCP-1
OT  - Mesenchymal stem cell
OT  - TRAIL
EDAT- 2016/01/07 06:00
MHDA- 2017/02/10 06:00
CRDT- 2016/01/07 06:00
PHST- 2015/09/28 00:00 [received]
PHST- 2015/12/27 00:00 [accepted]
PHST- 2016/01/07 06:00 [entrez]
PHST- 2016/01/07 06:00 [pubmed]
PHST- 2017/02/10 06:00 [medline]
AID - 10.1007/s13277-015-4746-7 [pii]
AID - 10.1007/s13277-015-4746-7 [doi]
PST - ppublish
SO  - Tumour Biol. 2016 Jun;37(6):8425-35. doi: 10.1007/s13277-015-4746-7. Epub 2016 
      Jan 5.