FIG 9.

HIF-2α-mediated neutrophil recruitment is essential for colon tumorigenesis. (A and B) Representative images of neutrophils (A) and quantification (B) of Ctrl pepducin (Veh)- or CXCR2 pepducin (PEP)-treated cells that migrated into the bottom well of a Transwell toward Hif-2α^+/+ and Hif-2α^LSL colon tissue explants. (C) qPCR analysis of Cxcl1 expression in CECs compared to IELs of Vhl^F/F and Vhl^ΔIE mice. (D) ELISA analysis of CXCL1 protein in colon tissues of Vhl^F/F (n = 6), Vhl^ΔIE (n = 3), and Vhl^ΔIE/Hif-2α^ΔIE (n = 4) mice. (E) Schematic diagram of AOM/DSS-induced CAC and CXCR2-pepducin treatment protocol. (F to J) Tumor counting (F) and tumor burden analysis (G), representative images of H&E staining and Ly6G staining (H) and Ki67 staining (I), and quantification of Ki67 staining (J) in colon tissue from Vhl^F/F (n = 4), Vhl^ΔIE plus Veh (n = 4), and Vhl^ΔIE plus PEP (n = 3) groups. *, P < 0.05, and **, P < 0.01 compared to Vhl^F/F; ##, P < 0.01 compared to Vhl^ΔIE plus CXCR2-pepducin. Statistical analysis was performed by one-way ANOVA, followed by Dunnett's multiple-comparison test. The error bars indicate standard deviations.