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. 2024 Sep 30;27(11):111085. doi: 10.1016/j.isci.2024.111085

Figure 3.

Figure 3

Mast cell-derived IL-10 promotes tumor development

(A) cDNA microarray analysis of the expression of IL-10 and its receptors IL-10RA and IL-10RB during the development of pancreatic cancer in KPC mice.

(B) Quantitative real-time PCR confirmed microarray data. Data are represented as mean ± SEM. A one-way ANOVA, followed by the Fisher’s least significant difference (LSD) multiple comparison test, shows the significances by ∗: p < 0.05; ∗∗: p < 0.01; ∗∗∗: p < 0.001; ∗∗∗∗: p < 0.0001.

(C) IL-10 production by mast cells (bar = 50 μm). Pancreas tissues were isolated from mast cell-deficient mice that were reconstituted with normal bone marrow derived mast cells (BMMC to Kit−/−; first row) or with BMMC derived from IL-10−deficient mice (MC (IL-10−/−) to Kit−/−; second row). Pancreatic tissues were also isolated from normal mice (NP) or KPC mice during the development of pancreatic cancer (CP, PanIN, PDAC). Sections were stained with anti-tryptase (left column, green) or anti-IL-10 (middle column, red). The right column represents the merged images.

(D) 28 days post implantation, mast cell-deficient mice reconstituted with IL-10−/− BMMC developed smaller tumors and less ascites than those reconstituted with wild-type BMMC. p = 0.0253 for tumor size and 0.014 for ascites incidence.

(E) KCLW mast cell-deficient mice were reconstituted with IL-10−/− BMMC. These animals survived longer than KCLW mice reconstituted with wild-type BMMC.

(F) Morphologic comparison of tumors that develop in mast cell-deficient mice reconstituted with IL-10−/− or wild-type BMMC. H&E staining (top left, bar = 500 μm) shows tumors implanted into Kit−/− mice reconstituted with IL-10−/− mast cells. H&E staining (top right, bar = 500 μm) shows tumors implanted into Kit−/− mice reconstituted with wild-type BMMC. Toluidine blue staining (center left, bar = 500 μm) shows tumors implanted into Kit−/− mice reconstituted with IL-10−/− mast cells. Toluidine blue staining (center right, bar = 500 μm) shows tumors implanted into Kit−/− mice reconstituted with wild-type BMMC. High power magnification (bottom left and right, bar = 50 μm) of Toluidine blue staining showed mast cells density in tumors. Yellow arrowheads illustrate representative toluidine blue stained mast cells. N = benign area with normal pancreatic structure, L = peripancreatic lymphoid tissue, and T = tumor.