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Journal: Frontiers in Immunology
Article Title: IGLC3 - tumor cells drive chemoresistance in colorectal cancer by polarizing SPP1 + macrophages via the CD44-Wnt-BTF3 axis
doi: 10.3389/fimmu.2026.1731216
Figure Lengend Snippet: IGLC3 - tumor cells promote SPP1 + macrophage polarization. (A) TSNE of 5 macrophage cell clusters in scRNA-seq of colorectal tumor tissues, including C1QC&LYVE1 + macrophages, C1QC + macrophages, C1QC&ISG15 + macrophages, ISG15 + macrophages and SPP1 + macrophages. (B) Heatmap of top differential gene expression between each macrophage subtypes. (C) Dot plot of inflammatory macrophages marker genes in each macrophage subtype. (D) The developmental trajectory between macrophage subtypes by monocle2 analysis. (E) Schematic diagram of macrophage and tumor cells co-culture model. (F) Heatmap of C1QC, LYVE1, SPP1 and ISG15 at mRNA level in THP-1 derived M0 macrophages co-cultured with vector and IGLC3 overexpressed HCT116/SW480 cells. The PBS treated THP-1 cells were set as control. (G) mRNA expression of CD206, IL-10 and Arg1 in patients derived SPP1 + macrophages (tumor tissues), and peripheral blood mononuclear cells derived M0 and M2 macrophages (blood). (H) Immunostaining of CD68 and SPP1 in patients derived colorectal tumor tissues. The CD68 and SPP1 + cells distribution was compared between patients with stage I~II (low stage) or stage III~IV (high stage), with metastasis or not, and responding to chemotherapy or not. (I) Volcano plot of differentially expressed cytokine-related genes between IGLC3 + and IGLC3 - tumor cells identified from our scRNA-seq dataset ( GSE166555 ). (J, K) Elisa of TGF-β and CXCL3 in supernatant of vector and IGLC3 overexpressed HCT116/SW480 cells. (L) mRNA expression of SPP1, ISG15, CD80 and CD68 in THP-1 derived M0 macrophages treated with TGF-β (10 ng/ml) and CXCL3 (50 ng/ml). All experiments were independently repeated at least three times with consistent results. Data are presented as mean ± SD, and statistical analyses were performed using t test. *p<0.05, **p<0.01.
Article Snippet: The following reagents were used:
Techniques: Gene Expression, Marker, Co-Culture Assay, Derivative Assay, Cell Culture, Plasmid Preparation, Control, Expressing, Immunostaining, Enzyme-linked Immunosorbent Assay