Figure 6. MMP7 Expression is Mediated by Stat3 in PDA Cells and Contributes to Tumor Size and Metastasis.

(A) Colo357 cells treated with compound S3I-201, a specific Stat3 inhibitor, or DMSO. Both MMP7 (qPCR) and p-Stat3 (Western blot) expression showed dose-dependent reduction. Means ± SD (N ≥ 3). ** p < 0.01, *** p < 0.001

(B) Number of Pdx1-Cre; Kras^G12D; MMP7^Het (N = 8) or Pdx1-Cre; Kras^G12D; MMP7^KO (N = 11) mice that were free of PDA found at time of death or at time of sacrifice at censor date. * p ≤ 0.05 (Chi-square). C-I, Characterization of Pdx1-Cre; Kras^G12D; p53^f/+; MMP7^Het and Pdx1-Cre; Kras^G12D; p53^f/+; MMP7^KO mice.

(C) Size of primary tumor at death (cm). Solid bar denotes mean. *** p < 0.001.

(D) Representative photograph of disease seen in Pdx1-Cre; Kras^G12D; p53^f/+; MMP7^Het cohort. Large pancreatic head mass is outlined in yellow dashed line. Yellow arrow points to mesenteric lymphadenopathy. Liver nodules and ascites were also seen at necropsy in this mouse.

(E) Pdx1-Cre; Kras^G12D; p53^f/+; MMP7^KO mouse. Yellow dashed line outlines relatively smaller pancreatic mass. * denotes massively dilated stomach and ** denotes dilated proximal duodenum. Arrowhead points to transition point (located next to tumor) from dilated proximal duodenum to decompressed distal bowel. There was no liver disease or obvious lymphadenopathy.

(F-G) H&E stains. Histology from both genotypes is similar.

(H) IHC for MMP7 Pdx1-Cre; Kras^G12D; p53^f/+; MMP7^Het, seen in patchy distribution.

(I) No MMP7 staining in Pdx1-Cre; Kras^G12D; p53^f/+; MMP7^KO tumors.

Scale bars, 100μm.

See also Figure S5 and Table S1.