Figure 4.

Duct obstruction promotes PDAC with a microenvironment similar to that seen in human PDAC. All images are distal to ligation. (A) CK19^CreERT2LSL-Kras^G12D pancreas stained with Gomori’s trichrome, which stains fibrillar collagen blue. Arrowheads, dense, well-organized collagen bundles not in contact with dysplasia, whereas dysplastic and invasive regions are in contact with poorly organized collagen. (B) Alcian blue, pH 2.5, labels myxoid stroma (bracket) as well as a small number of ductal lesions (arrows). (C) Matrix remodeling protein periostin (brown) surrounding dysplastic and invasive lesions but scarce surrounding cytologically normal lesions (upper right corner). (D) Myofibroblasts labeled for αSMA (brown) are concentrated around dysplastic and invasive lesions but not cytologically normal lesions. (E) Macrophages labeled with F4/80 antibody (brown) are widely dispersed throughout distal pancreas. (F) Extracellular matrix protein fibronectin (brown) forming parallel bundles (bracket) around invading cells (arrowheads). (G and H) Macrophages (labeled for F4/80 in red) and myofibroblasts (labeled for αSMA in green) show the shift in distribution of myofibroblasts from cytologically normal lesions (G, lower right) with few surrounding myofibroblasts to atypic lesions with increased myofibroblast accumulation (G, upper left) to widespread distribution in areas of invasion (H), whereas macrophages are broadly distributed throughout. (G’ and H’) show αSMA labeling alone. (G” and H”) show F4/80 alone. Size bars, 100 μm.