2. Academic Validation
  3. Expression of programmed death ligand 1 (PD-L1) is associated with metastasis and differentiation in gastric cancer

Expression of programmed death ligand 1 (PD-L1) is associated with metastasis and differentiation in gastric cancer

  • Life Sci. 2020 Feb 1;242:117247. doi: 10.1016/j.lfs.2019.117247.
Peng-Xing He 1,  Zhi-Lu Ma 2,  Huan Han 2,  Xu-Yang Zhang 2,  Sheng-Hui Niu 2,  Lin-Na Du 2,  Yi-Chao Zheng 3,  Hong-Min Liu 4
Affiliations

Affiliations

  • 1 Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, PR China.. Electronic address: hepengxing@zzu.edu.cn.
  • 2 Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, PR China.
  • 3 Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, PR China.. Electronic address: yichaozheng@zzu.edu.cn.
  • 4 Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, PR China.. Electronic address: liuhm@zzu.edu.cn.
PMID: 31899223 DOI: 10.1016/j.lfs.2019.117247
Abstract

Aims: Programmed death ligand 1 (PD-L1, CD274) has been reported to be expressed abnormally in many cancers, nevertheless, effect of PD-L1 on tumor cells remains unclear, especially in gastric Cancer (GC). This study aimed to investigate the role of PD-L1 in metastasis and differentiation in GC.

Main methods: Immunohistochemistry was performed on 237 paired GC tissues. shPD-L1 cells were generated by lentivirus shRNA solution and PD-L1-overexpressing cells were constructed by pcDNA3.1. Expression of PD-L1 and E-cadherin in GC cells were detected by western blot.

Key findings: PD-L1 expression was significantly lower in GC than that in adjacent normal tissues, especially in poorly differentiated and metastatic GC, but was positively correlated to survival time of patients. Moreover, PD-L1 ablation could decrease E-cadherin expression, promote cell migration and wound repair ability. In turn, overexpression of PD-L1 increased E-cadherin expression and inhibited wound repair ability. At the same time, All-trans retinoic acid (ATRA), which has the properties of pro-differentiation and inhibition of invasion and metastasis, upregulated the expression of PD-L1 and E-cadherin.

Significance: These findings not only identify PD-L1 may have a positive role for the treatment of GC, but also implicate that ATRA combined PD-L1 antibody drugs may enhance anti-tumor Immunity in GC.

Keywords

All-trans retinoic acid (ATRA); Differentiation; Gastric cancer (GC); Metastasis; Programmed death ligand 1(PD-L1).

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