PMID- 35119076
OWN - NLM
STAT- MEDLINE
DCOM- 20220211
LR  - 20220531
IS  - 1791-2431 (Electronic)
IS  - 1021-335X (Print)
IS  - 1021-335X (Linking)
VI  - 47
IP  - 4
DP  - 2022 Apr
TI  - Enhanced CXCL12/CXCR4 signaling increases tumor progression in 
      radiation‑resistant pancreatic cancer.
LID - 68 [pii]
LID - 10.3892/or.2022.8279 [doi]
AB  - Pancreatic cancer (PaCa) exhibits one of the poorest prognoses among all 
      gastrointestinal cancers due to the rapid development of treatment resistance, 
      which renders chemotherapy and radiotherapy no longer effective. However, the 
      mechanisms through which PaCa becomes resistant to radiotherapy are unknown. 
      Here, we established radiation‑resistant PaCa cell lines to investigate the 
      factors involved in radiation resistance. The role of the C‑X‑C motif chemokine 
      ligand 12 (CXCL12)/C‑X‑C chemokine receptor type 4 (CXCR4) axis in radiation 
      resistance in PaCa and the effects of a CXCR4 antagonist on radiation‑resistant 
      PaCa cell lines were investigated. As confirmed by immunofluorescence staining, 
      reverse transcription quantitative polymerase chain reaction, and western 
      blotting, the expression of CXCR4 was higher in radiation‑resistant PaCa cell 
      lines than that noted in normal PaCa cell lines. The invasion ability of 
      radiation‑resistant PaCa cell lines was greater than that of normal cell lines 
      and was enhanced by CXCL12 treatment and coculture with fibroblasts; this 
      enhanced invasion ability was suppressed by the CXCR4 antagonist AMD070. 
      Irradiation after treatment with the CXCR4 antagonist suppressed the colonization 
      of radiation‑resistant PaCa cell lines. In conclusion, the CXCL12/CXCR4 axis may 
      be involved in the radiation resistance of PaCa. These findings may facilitate 
      the development of novel treatments for PaCa.
FAU - Kato, Tomokatsu
AU  - Kato T
AD  - Department of Gastroenterological Surgery, Nagoya City University Graduate School 
      of Medical Sciences, Nagoya, Aichi 467‑8601, Japan.
FAU - Matsuo, Yoichi
AU  - Matsuo Y
AD  - Department of Gastroenterological Surgery, Nagoya City University Graduate School 
      of Medical Sciences, Nagoya, Aichi 467‑8601, Japan.
FAU - Ueda, Goro
AU  - Ueda G
AD  - Department of Gastroenterological Surgery, Nagoya City University Graduate School 
      of Medical Sciences, Nagoya, Aichi 467‑8601, Japan.
FAU - Murase, Hiromichi
AU  - Murase H
AD  - Department of Gastroenterological Surgery, Nagoya City University Graduate School 
      of Medical Sciences, Nagoya, Aichi 467‑8601, Japan.
FAU - Aoyama, Yoshinaga
AU  - Aoyama Y
AD  - Department of Gastroenterological Surgery, Nagoya City University Graduate School 
      of Medical Sciences, Nagoya, Aichi 467‑8601, Japan.
FAU - Omi, Kan
AU  - Omi K
AD  - Department of Gastroenterological Surgery, Nagoya City University Graduate School 
      of Medical Sciences, Nagoya, Aichi 467‑8601, Japan.
FAU - Hayashi, Yuichi
AU  - Hayashi Y
AD  - Department of Gastroenterological Surgery, Nagoya City University Graduate School 
      of Medical Sciences, Nagoya, Aichi 467‑8601, Japan.
FAU - Imafuji, Hiroyuki
AU  - Imafuji H
AD  - Department of Gastroenterological Surgery, Nagoya City University Graduate School 
      of Medical Sciences, Nagoya, Aichi 467‑8601, Japan.
FAU - Saito, Kenta
AU  - Saito K
AD  - Department of Gastroenterological Surgery, Nagoya City University Graduate School 
      of Medical Sciences, Nagoya, Aichi 467‑8601, Japan.
FAU - Morimoto, Mamoru
AU  - Morimoto M
AD  - Department of Gastroenterological Surgery, Nagoya City University Graduate School 
      of Medical Sciences, Nagoya, Aichi 467‑8601, Japan.
FAU - Ogawa, Ryo
AU  - Ogawa R
AD  - Department of Gastroenterological Surgery, Nagoya City University Graduate School 
      of Medical Sciences, Nagoya, Aichi 467‑8601, Japan.
FAU - Takahashi, Hiroki
AU  - Takahashi H
AD  - Department of Gastroenterological Surgery, Nagoya City University Graduate School 
      of Medical Sciences, Nagoya, Aichi 467‑8601, Japan.
FAU - Takiguchi, Shuji
AU  - Takiguchi S
AD  - Department of Gastroenterological Surgery, Nagoya City University Graduate School 
      of Medical Sciences, Nagoya, Aichi 467‑8601, Japan.
LA  - eng
PT  - Journal Article
DEP - 20220204
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (CXCL12 protein, human)
RN  - 0 (CXCR4 protein, human)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Receptors, CXCR4)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cell Movement
MH  - Cell Proliferation
MH  - *Chemokine CXCL12/genetics
MH  - Fibroblasts
MH  - Humans
MH  - Pancreas
MH  - *Pancreatic Neoplasms/drug therapy/genetics/radiotherapy
MH  - Radiation Tolerance
MH  - *Receptors, CXCR4/genetics
MH  - Signal Transduction
PMC - PMC8848476
OTO - NOTNLM
OT  - CXCL12
OT  - CXCR4
OT  - CXCR4 antagonist
OT  - pancreatic cancer
OT  - radiation‑resistant
COIS- The authors declare that they have no competing interests.
EDAT- 2022/02/05 06:00
MHDA- 2022/02/12 06:00
PMCR- 2022/02/03
CRDT- 2022/02/04 08:41
PHST- 2021/10/21 00:00 [received]
PHST- 2022/01/20 00:00 [accepted]
PHST- 2022/02/04 08:41 [entrez]
PHST- 2022/02/05 06:00 [pubmed]
PHST- 2022/02/12 06:00 [medline]
PHST- 2022/02/03 00:00 [pmc-release]
AID - 68 [pii]
AID - OR-47-04-08279 [pii]
AID - 10.3892/or.2022.8279 [doi]
PST - ppublish
SO  - Oncol Rep. 2022 Apr;47(4):68. doi: 10.3892/or.2022.8279. Epub 2022 Feb 4.