Abstract
BACKGROUND: The tumor microenvironment (TME) plays an important role in regulating gastric cancer (GC) progression. The infiltration of M0 macrophages into the TME negatively affects the prognosis of patients with various tumors. METHODS: The data were obtained from the TCGA and GEO databases and our hospital (107 patients). The expression of IQGAP3 was knocked down in AGS and NCI-N87 GC cells. Cell proliferation, migration, and invasion assays were performed. RNA sequencing was performed on GC cells with different IQGAP3 expression. AGS and THP-1 cells were mixed to create a co-cultured subcutaneous tumor model in nude mice. Tumor growth in the mice was observed by using luciferin fluorescence and the tumor tissues were subjected to immunohistochemistry. RESULTS: The expression of IQGAP3 was increased in GC tissues (P < 0.001) and was associated with infiltration of M0 macrophages and a poor prognosis for GC patients (P < 0.01). Knockdown of IQGAP3 resulted in decreased expression of CXCL13 (P < 0.001) and less phosphorylation of pSTAT3 and pERK1/2 (P < 0.001). The expression of CXCL13 was decreased after the pSTAT3 and pERK1/2 phosphorylation inhibitors were added. In the co-culture experiment, the M0/THP-1 ratio decreased significantly in the low-IQGAP3-expression group (P < 0.001). However, adding recombinant human CXCL13 proteins to the low IQGAP3 expression group increased the M0/THP-1 ratio. In vivo, tumor growth and M0 macrophage infiltration were both suppressed in the group with low IQGAP3 expression. CONCLUSION: IQGAP3 is a potential pro-carcinogenic factor in GC. IQGAP3 promotes the expression and secretion of CXCL13 via the ERK1/2 and STAT3 pathways, thereby causing M0 macrophages to infiltrate the TME.