Dextran sulfate inhibits the invasion, migration, and programmed death ligand 1 expression in human gastric cancer cells by affecting the M2 tumor-associated macrophages polarization

Jing Shang¹Yuanyi Xu²Yuejia Tao²Bing Li²Mengqi Li²Jiaxin Guo²Lvjun Yan¹Yunning Huang^3*

• ¹University-Town Hospital of Chongqing Medical University, Chongqing, China
• ²Third Clinical Medical College, Ningxia Medical University, Yinchuan, China
• ³The Affiliated Hospital of Ningxia Medical College, Ningxia, CHINA, Ningxia, China

Objective To investigate Dextran Sulfate's role in the M0 to M2 macrophage polarization and its effect on programmed death ligand1 (PD-L1) expression, invasion, migration, proliferation, and apoptosis of human gastric cancer cells (HGCC), via its action on M2 tumor-associated macrophages (M2-TAMs). Methods: The effects of DS on M0-to-M2 macrophage polarization and HGCC behavior were examined. CD163 expression was analyzed to determine macrophage polarization, whereas HGCC proliferation, apoptosis, migration, invasion, and PD-L1 expression were quantified. The effect of DS on tumor development was evaluated in an in vivo nude mice model of intraperitoneal implantation by assessing the size and number of implanted nodules. The study also analyzed the association between tumor CD163 and PD-L1 expression. Results DS inhibited M0-to-M2 macrophage polarization, HGCC proliferation, invasion, and migration while increasing apoptosis and decreasing PD-L1 expression.DS lowered the number and size of metastatic tumor nodules in nude mice while decreasing CD163 expression. CD163 expression is positively associated with PD-L1 expression (P < 0.01, R2 = 0.1613, N = 46). Conclusion DS inhibits the macrophage transition to the M2 phenotype, leading to reduced PD-L1 expression and HGCC cell proliferation, invasion, and migration while increasing cell death.