Figure 6. 2G8 promotes an epithelial phenotype in murine tumors in vivo.

A-E, LSL-Kras^G12D; Cdkn2a^lox/lox; p48^Cre (KIC) mice establish tumors and precursor PanIN lesions by 4 weeks old. Mice at this timepoint were randomized to receive saline (Control), gemcitabine (Gem), 2G8 or 2G8 + Gem for 4 weeks. A, Analysis of tumor architecture using Hemotoxylin and Eosin staining (scale bar, 100 µm). 2G8 treated tumors were noted to have significantly more PanIN and epithelial lesions than the mice treated with Gem or Control. B, This was confirmed with PAS-Alcian Blue staining that marks mucin-secreting PanIN lesions but not invasive lesions (PAS-Alcian Blue, purple; scale bar, 100 µm). Additionally, 2G8 tumors had significantly increased Ecad expression (C) and decreased vimentin expression (D) by immunohistochemistry. E, Representative images of these tumors demonstrate the predominant epithelial phenotype of 2G8-treated tumors (Ecad red, vimentin green; scale bar, 50 µm). F and G, 2G8 induces a similar epithelial phenotype in Pan02 tumors. Immunohistochemical analysis of β-catenin (F) and E-cadherin (Ecad, G) in Pan02 tumors treated with control, Gem, 2G8 or 2G8+GEM. Bar graphs represent mean+/−SEM. **, p<0.01; #, p<0.0001 vs. control; ^^, p<0.001; ^^^, p<0.0001 vs. Gem.