Conditional medium of gastric cancer mesenchymal stem cells promotes PD-L1 expression in gastric cancer cells and tumor growth via upregulating VGLL4].

Objective To investigate whether conditional medium of gastric cancer mesenchymal stem cells (GCMSCs-CM) could up-regulate the expression of programmed death 1 ligand 1 (PD-L1) and promote gastric cancer progression by vestigial-like protein 4 (VGLL4). Methods Western blot was used to detect the expression of VGLL4 in SGC-7901, HGC-27 and MGC-803 gastric cancer cells. The expression of VGLL4 in HGC-27 and SGC-7901 cells was inhibited by being transfected with VGLL4 specific siRNA and plasmid was used to overexpress VGLL4 in SGC-7901 cells. The gastric cancer cells were divided into control group, GCMSCs-CM treatment group, VGLL4 interference or overexpression group, and VGLL4 interference followed by GCMSCs-CM treatment group. The expression of PD-L1 in each group was detected by Western blot and real time quantitative PCR (qRT-PCR). The proliferation of SGC-7901 cells was detected by colony formation assay. The migration of SGC-7901 cells was detected by TranswellTM migration assay. Human peripheral blood mononuclear cells adoptive NCG immunodeficiency mouse (PBMCs-NCG) subcutaneous tumor model was constructed to observe the tumor growth in mice. The mice were divided into control group, GCMSCs-CM treatment group, VGLL4 knockdown group, and VGLL4 knockdown followed by GCMSCs-CM treatment group. VGLL4 and PD-L1 mRNA levels of tumor tissue were detected by qRT-PCR. Immunohistochemical staining was used to detect the expression of VGLL4, PD-L1, ki67, CD8 and granzyme B (GZMB). Results VGLL4 is expressed in SGC-7901, HGC-27 and MGC-803 cells. The expression of PD-L1 mRNA and protein decreased significantly in SGC-7901 and HGC-27 cells transfected with siVGLL4. The expression of PD-L1 mRNA and protein was up-regulated after overexpression of VGLL4 in SGC-7901 cells. The expression of VGLL4 increased after GCMSCs-CM treatment of HGC-27 and MGC-803 cells. Inhibition of VGLL4 in HGC-27 could reverse the up-regulation of PD-L1 by GCMSCs-CM. Inhibition of VGLL4 in SGC-7901 weakened the ability of GCMSCs-CM to promote cell proliferation and migration. Knockdown of VGLL4 inhibited the effect of GCMSCs-CM in promoting tumor growth in mice and enhanced the anti-tumor immunity of PBMCs-NCG mice. Conclusion GCMSCs-CM promotes the expression of PD-L1 and tumor growth by upregulating VGLL4 in gastric cancer cells.

Citation

Ying Ding, Wei Zhu, Qianqian Wang, Bin Chen, Mei Wang, Yuanyuan Zhao. Conditional medium of gastric cancer mesenchymal stem cells promotes PD-L1 expression in gastric cancer cells and tumor growth via upregulating VGLL4]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology. 2022 Apr;38(4):321-327

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PMID: 35583061

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