Figure 5.

Secretory leukocyte protease inhibitor (SLPI) expression increases aggressiveness of Hey‐A8 orthotopic xenografts. (A) Wild type (WT)/SLPI and protease‐inhibitor null (PI‐)/SLPI transfectants induce greater tumor burden than mock transfected Hey‐A8 cells. Animal weight was used as a surrogate for tumor burden; animals were weighed at indicated times after inoculation and weight compared statistically across groups at each time point. Data presented are 10 animals/group from the second of 2 experiments. (B) Representative pictures of intraperitoneal disease. Peritoneal nodules were found in all inoculated mice (a). Solid omental and mesenteric disease (b) and macroscopic serosal liver nodules (c) were seen in the WT/SLPI and PI‐mutants. (C) Local invasion was seen with the PI‐/SLPI mutants (50 × magnification). (D, E) Higher proliferative index in WT/SLPI and PI‐/SLPI mutants. Ki‐67 staining of available sections from mock (n= 4) WT/SL Pl (n= 5), PI‐/SLPI mutants F‐SLPI (n= 5) and R‐SLPI (n= 5) tumors are shown, (representative stains), (D) and Ki‐67‐positive nuclei counted (E). At least 200 cells in three random fields were counted per tumor sections (P ≤ 0.02). (F) Increased progranulin (PRGN) is found in SLPI overexpressors. PRGN immunostain was done on available xenograft fixed sections and representative examples are shown. Note staining in invasive cells (arrows). F‐SLPI, PI‐/SLPI mutant Leu72Phe; R‐SLPI, PI‐/SLPI mutant Leu72Arg. H&E, hematoxylin and eosin.