Preliminary research on the pathological role of cathepsin-B in subcutaneous heteroplastic pancreatic carcinoma in nude mice

Background Cathespin-B （cath-B） is an important proteolytic enzyme involved in the disease course of invasion in many types of cancer. Cath-B expression in subcutaneous heteroplastic pancreatic carcinoma in nude mice has not been studied. We investigated the role of cath-B in a model of heteroplastic pancreatic carcinoma in BALB/c nude mice. Methods Thirty-two six-week-old female BALB/c nude mice were equally divided into four groups. PANC-1 cells were inoculated subcutaneously in the left axillary region. Besides volume, weight of subcutaneous tumor, and change in body weight, cath-B expression in each group was measured by immunohistochemical staining, PCR and Western blotting. Its relationship to microvessel density （MVD）, CD44v6, and placenta growth factor （PLGF） was also examined. CA-074Me, a specific inhibitor of cath-B, was injected intraperitoneally （i.p.） at different stages of tumor growth in group B and C. Gemcitabine （GEM）, was also injected （i.p.） in group D to compare anti-tumor efficacy with CA-074Me. Results Expression of cath-B at different levels was related to tumor growth, MVD, and PLGF expression. In group A （control group）, cath-B expression was enhanced more than that seen in other groups. CA-074Me clearly inhibited cath-B expression and tumor growth in group B. There was no difference between group C and D with respect to anti-tumor effect. Conclusions Cath-B correlates with the growth and angiogenesis of tumors, but not with the adhesion induced by CD44v6. CA-074Me clearly inhibited cath-B expression and demonstrated an anti-neoplastic and anti-angiogenesis effect.