Figure 6.

IL1R2 neutralization inhibited breast tumorigenesis. A) BMI1 and IL1R2 protein expression were downregulated in a dose‐dependent manner after IL1R2‐neutralizing antibody treatment (cIgG, control IgG group). B) Neutralizing antibody (3 µg mL⁻¹) pretreatment increased BC cell chemosensitivity to docetaxel (*, p < 0.05; **, p < 0.01 vs cIgG group). C) Neutralizing antibody (3 µg mL⁻¹) pretreatment inhibited self‐renewal of SUM149 cells. D) BTIC population was declined after being treated with neutralizing antibody (3 µg mL⁻¹) (*, p < 0.05 vs cIgG group). E,F) Neutralizing antibody pretreatment for 7 days inhibited SUM149 xenograft tumor growth (*, p < 0.05; **, p < 0.01 vs cIgG group). G) The stem cell frequency in SUM149 xenograft tumors was calculated by the limited dilution assay (*, p < 0.05; **, p < 0.01 vs cIgG group). H,I) Neutralizing antibody treatment in vivo inhibited SUM149 xenograft tumor growth when combined with/without docetaxel in NOD/SCID female mice (*, p < 0.05; **, p < 0.01). Time points of antibody intraperitoneal injection are indicated by arrows. J,K) IHC analysis results showed that IL1R2‐ and BMI1‐positive cells were decreased in the neutralizing antibody and docetaxel combination group (*, p < 0.05; **, p < 0.01) (representative images were shown, 200×). L) Single cells from the SUM149 xenografts from indicated groups were isolated and reinjected to the fat pad of nude mice; the frequency of BTIC was calculated based on the positive sites per groups. M) Neutralizing antibody treatment in vivo inhibited PDX tumor growth in NOD/SCID female mice (**, p < 0.01). Time points of antibody intraperitoneal injection are indicated by arrows. L,N) Single cells from the PDX tumors from indicated groups were isolated and reinjected to the fat pad of nude mice; the frequency of BTIC was calculated based on the positive sites per groups. O) Proposed model depicts the molecular mechanism that IL1R2 regulates BTIC self‐renewal and BC progression.