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.
Zhang
Chong
C
Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
Sun
Jia-bang
JB
Liu
Da-chuan
DC
Cui
Ye-qing
YQ
Liu
Shuang
S
Sun
Hai-chen
HC
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015153:Blotting, Western; D001835:Body Weight; D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D045744:Cell Line, Tumor; D004151:Dipeptides / Q000627:therapeutic use; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; C400541:CA 074 methyl ester; D004151:Dipeptides; C000608036:PGF protein, human; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D000072483:Placenta Growth Factor; D002401:Cathepsin B