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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