Induction of Metastatic Gastric Cancer by Peroxisome Proliferator-Activated Receptorδ Activation

Figure 2

Pathophysiology of gastric tumorigenesis. (A) Histological changes in the forestomach after GW501516 and/or DMBA treatment. Upper panel: Stereoscopic images of H&E stained sections of the stomach in (a) untreated, (b) DMBA-treated, (c, d) DMBA plus GW501516-treated mice, and (e) metastases of the abdominal wall. Lower panel: higher magnification (200x) of the boxes in areas in the upper panel. Insets, magnification 400x. (a) Morphology of the normal forestomach wall. (b) Squamous epithelial hyperplasia, where the basal membrane is well defined. (c) Squamous cell carcinoma. (d) Invasive squamous cell carcinoma showing disruption of the basement membrane. (e) Metastatic squamous carcinoma showing invasion into the abdominal wall. (B) Histological changes in the stomach and esophagus after treatment with either GW501516 or DMBA. H&E sections of the forestomach wall (a, b, c) and esophagus (d, e, f) six months after administration of GW501516 or five months after treatment with DMBA. Both GW501516 and DMBA were associated with increased keratinization (*) of squamous epithelium (arrow). Magnification 400x. (C) Cytokeratin 14 (CK14) and cytokeratin18 (CK18) expression in gastric tissue and tumors. Squamous epithelium of the forestomach (a), gastric mucosa (b), and gastric tumors (c, d). Tumors are CK14⁺/CK18^- indicating a squamous epithelial origin. Magnification 200x, insets, 400x.