PMID- 37193135
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230519
IS  - 1943-8141 (Print)
IS  - 1943-8141 (Electronic)
IS  - 1943-8141 (Linking)
VI  - 15
IP  - 4
DP  - 2023
TI  - CXCL5 knockdown attenuated gemcitabine resistance of pancreatic cancer through 
      regulation of cancer cells and tumour stroma.
PG  - 2676-2689
AB  - Chemoresistance is one of the major causes to the poor prognosis of pancreatic 
      cancer (PC). Gemcitabine alone and gemcitabine-based therapies are mostly used 
      for the treatment of PC. Gemcitabine resistance becomes the focus of 
      chemotherapy. C-X-C motif chemokine 5 (CXCL5), a member of the C-X-C chemokine 
      family, acts through C-X-C chemokine receptor type 2 (CXCR2). A high level of 
      CXCL5 is associated with worse prognosis in PC patients and increased suppressive 
      immune cell infiltration. Increased expression of CXCL5 is also found in 
      gemcitabine-treated PC cells. To investigate the role of CXCL5 in PC response to 
      gemcitabine, CXCL5 knockdown (KD) PC cells were generated and its effect on 
      cancer cell response to gemcitabine in vitro and in vivo was studied. The 
      mechanisms involved were also explored by determining the changes in the tumour 
      microenvironment (TME) and protein profile of the CXCL5 KD cells using 
      immune-staining and proteomic analysis. The results showed that CXCL5 expression 
      were increased in all PC cell lines tested and in gemcitabine-resistant tumour 
      tissue, that CXCL5 KD suppressed PC growth and sensitized PC cell response to 
      gemcitabine and that CXCL5 KD stimulated the activation of stromal cells in TME. 
      We conclude that CXCL5 promotes gemcitabine resistance by affecting TME and 
      cancer cells.
CI  - AJTR Copyright (c) 2023.
FAU - Lee, Nien-Hung
AU  - Lee NH
AD  - Department of Surgery, University of Melbourne, Austin Health Heidelberg, 
      Victoria, Australia.
FAU - Ma, Yi
AU  - Ma Y
AD  - Department of Surgery, University of Melbourne, Austin Health Heidelberg, 
      Victoria, Australia.
FAU - Ang, Ching-Seng
AU  - Ang CS
AD  - Bio-21 Institute, University of Melbourne Parkville, Victoria, Australia.
FAU - Dumesny, Chelsea
AU  - Dumesny C
AD  - Department of Surgery, University of Melbourne, Austin Health Heidelberg, 
      Victoria, Australia.
FAU - Huynh, Nhi
AU  - Huynh N
AD  - Department of Surgery, University of Melbourne, Austin Health Heidelberg, 
      Victoria, Australia.
AD  - Tumour Targeting Laboratory, Level 5, ONJCRI Heidelberg, Victoria, Australia.
FAU - Yang, Yang
AU  - Yang Y
AD  - Department of Surgery, University of Melbourne, Austin Health Heidelberg, 
      Victoria, Australia.
FAU - Wang, Kai
AU  - Wang K
AD  - Department of Surgery, University of Melbourne, Austin Health Heidelberg, 
      Victoria, Australia.
FAU - Nikfarjam, Mehrdad
AU  - Nikfarjam M
AD  - Department of Surgery, University of Melbourne, Austin Health Heidelberg, 
      Victoria, Australia.
FAU - He, Hong
AU  - He H
AD  - Department of Surgery, University of Melbourne, Austin Health Heidelberg, 
      Victoria, Australia.
LA  - eng
PT  - Journal Article
DEP - 20230415
PL  - United States
TA  - Am J Transl Res
JT  - American journal of translational research
JID - 101493030
PMC - PMC10182491
OTO - NOTNLM
OT  - CXCR2
OT  - CXL5
OT  - collagen I
OT  - gemcitabine
OT  - tumour stroma
OT  - alpha-SMA
COIS- None.
EDAT- 2023/05/17 01:07
MHDA- 2023/05/17 01:08
PMCR- 2023/04/15
CRDT- 2023/05/16 21:20
PHST- 2022/07/26 00:00 [received]
PHST- 2022/12/28 00:00 [accepted]
PHST- 2023/05/17 01:08 [medline]
PHST- 2023/05/17 01:07 [pubmed]
PHST- 2023/05/16 21:20 [entrez]
PHST- 2023/04/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Transl Res. 2023 Apr 15;15(4):2676-2689. eCollection 2023.