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 t...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.展开更多
基金National Natural Science Foundation of China(no.82372860,no.81641098)Peking University First Hospital Youth Clinical Research Project(no.2021CR03)+3 种基金Peking University First Hospital Multidisciplinary Research Project(no.2022CR13)the Youth Cultivated Research Fund of Peking University Health Center(grant no.BMU2020PYB026)National Project for Clinical Key Specialty DevelopmentTianjin Key Medical Discipline Construction Project(grant no.TJYXZDXK-3-003A).
文摘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.
