PMID- 32914185
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20220531
IS  - 1526-4637 (Electronic)
IS  - 1526-2375 (Linking)
VI  - 21
IP  - 12
DP  - 2020 Dec 25
TI  - Pain May Promote Tumor Progression via Substance P-Dependent Modulation of 
      Toll-like Receptor-4.
PG  - 3443-3450
LID - 10.1093/pm/pnaa265 [doi]
AB  - BACKGROUND: In a previous study, persistent pain was suggested to be a risk 
      factor for tumor patients. However, the mechanism underlying this phenomenon is 
      still unclear. Substance P (SP), a pain-related neuropeptide secreted by the 
      neural system and the immune system, plays an important role in the induction and 
      maintenance of persistent pain. METHODS: In this study, in order to explore 
      whether SP participates in the influence of pain on tumor progression, the serum 
      samples of lung cancer and breast cancer patients were collected and tested. An 
      elevated expression of SP was found in patients with pain. RESULTS: Cell 
      pharmacological experiments revealed that SP can upregulate the expression of 
      Toll-like receptor-4 (TLR-4) in tumor cells and increase the proliferation, 
      migration, and invasive activity of tumor cells. As high expression of TLR-4 has 
      the ability to enhance the biological activity of tumor cells, TLR-4 is thought 
      to be involved in SP-induced tumor proliferation, migration, and invasion. 
      Treatment of tumor cells with Aprepitant, a specific blocker of the NK-1 
      receptor, could reduce the expression of TLR-4 and reduce the proliferation, 
      invasion, and migration activities of tumor cells; further proof of the influence 
      of SP on TLR-4 expression depends on the NK-1 receptor located in tumor cells. 
      CONCLUSIONS: Based on the results above, we proposed a possible mechanism 
      underlying pain affecting tumor progression: The presence of pain increases the 
      content of SP in patients' blood, and elevated SP increases the expression of 
      tumor TLR-4 by acting on the NK-1 receptor, which ultimately affects the 
      biological activity of the tumor.
CI  - (c) The Author(s) 2020. Published by Oxford University Press on behalf of the 
      American Academy of Pain Medicine. All rights reserved. For permissions, please 
      e-mail: journals.permissions@oup.com.
FAU - Yang, Chao
AU  - Yang C
AD  - Translational Institute for Cancer Pain, Xinhua Hospital Affiliated to Shanghai 
      Jiao Tong University School of Medicine, Chongming Branch, Shanghai, China.
FAU - Sun, Yunheng
AU  - Sun Y
AD  - State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, 
      Ren Ji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 
      Shanghai, China.
FAU - Ouyang, Xueyan
AU  - Ouyang X
AD  - Translational Institute for Cancer Pain, Xinhua Hospital Affiliated to Shanghai 
      Jiao Tong University School of Medicine, Chongming Branch, Shanghai, China.
FAU - Li, Jing
AU  - Li J
AD  - Henan Provincial People's Hospital, Zhengzhou, China.
FAU - Zhu, Zhen
AU  - Zhu Z
AD  - Translational Institute for Cancer Pain, Xinhua Hospital Affiliated to Shanghai 
      Jiao Tong University School of Medicine, Chongming Branch, Shanghai, China.
FAU - Yu, Ruihua
AU  - Yu R
AD  - Translational Institute for Cancer Pain, Xinhua Hospital Affiliated to Shanghai 
      Jiao Tong University School of Medicine, Chongming Branch, Shanghai, China.
FAU - Wang, Li
AU  - Wang L
AD  - Translational Institute for Cancer Pain, Xinhua Hospital Affiliated to Shanghai 
      Jiao Tong University School of Medicine, Chongming Branch, Shanghai, China.
FAU - Jia, Lin
AU  - Jia L
AD  - Shanghai International Medical Center, Shanghai, China.
FAU - Ding, Gang
AU  - Ding G
AD  - Shanghai International Medical Center, Shanghai, China.
FAU - Wang, Yaosheng
AU  - Wang Y
AD  - Translational Institute for Cancer Pain, Xinhua Hospital Affiliated to Shanghai 
      Jiao Tong University School of Medicine, Chongming Branch, Shanghai, China.
FAU - Jiang, Feng
AU  - Jiang F
AD  - Translational Institute for Cancer Pain, Xinhua Hospital Affiliated to Shanghai 
      Jiao Tong University School of Medicine, Chongming Branch, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Pain Med
JT  - Pain medicine (Malden, Mass.)
JID - 100894201
RN  - 0 (Receptors, Neurokinin-1)
RN  - 0 (TLR4 protein, human)
RN  - 0 (Toll-Like Receptor 4)
RN  - 33507-63-0 (Substance P)
SB  - IM
MH  - Humans
MH  - *Neoplasms
MH  - Pain
MH  - Receptors, Neurokinin-1
MH  - *Substance P
MH  - Toll-Like Receptor 4
OTO - NOTNLM
OT  - Pain
OT  - Substance P
OT  - TLR-4
OT  - Tumor Progression
EDAT- 2020/09/12 06:00
MHDA- 2021/05/15 06:00
CRDT- 2020/09/11 05:46
PHST- 2020/09/12 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2020/09/11 05:46 [entrez]
AID - 5903930 [pii]
AID - 10.1093/pm/pnaa265 [doi]
PST - ppublish
SO  - Pain Med. 2020 Dec 25;21(12):3443-3450. doi: 10.1093/pm/pnaa265.