Figure 2. Overexpression of heparanase confers increased susceptibility to colitis-associated tumors in AOM/DSS-treated and DSS-treated mice.

(A–F) AOM/DSS-treated mice. (G and H) DSS-treated mice. (A) Gross appearance. Colons (n = 9) were removed on day 110 from AOM/DSS-treated mice, opened longitudinally, washed in PBS, and photographed. (B) Sub-gross examination (original magnification, ×3) and (C) quantification of colonic tumors detected on day 110 (AOM/DSS-treated mice) revealed increased tumor incidence (C, top) and burden (C, bottom) in Hpa Tg colon (gray bars) versus WT colon (black bars) (n = 9). (D) Immunostaining with anti–β-catenin antibody reveals enhanced expression and nuclear localization of β-catenin in Hpa Tg (bottom) versus WT (top) colonic tumors (original magnification, ×400). (E and F) Increased vascular density in Hpa Tg versus WT colonic tumors evaluated by immunostaining with anti-CD31 antibody (original magnification, ×400) (E) and quantified by blind counting of blood vessels per microscopic field (F). (G and H) DSS-induced chronic colitis (without AOM administration) results in colonic tumor formation in Hpa Tg but not in WT mice. (G) Representative microphotographs of histological sections showing the presence of tumors in colons derived from Hpa Tg (bottom) but not WT (top) mice. Magnification, ×100; inset: boxed regions shown at higher magnification (×400). (H) Number of tumors per colon (top) and percentage of tumor-bearing animals (bottom) in Hpa Tg versus WT mice. Error bars represent mean ± SD. *P < 0.05, **P < 0.01.