Synthetic matrix metalloproteinase inhibitor, BB-94, inhibits the invasion of neoplastic human prostate cells in a mouse model.
BACKGROUND
It has been suggested that increased metalloproteinase activity is a critical event in neoplastic progression leading to the initiation of local invasion and ultimately to the dissemination of neoplastic cells. This has led to an interest in testing the ability of metalloproteinase inhibitors to prevent the progression of carcinoma in situ into invasive and, therefore, more malignant tumors. One such agent is the synthetic matrix metalloproteinase inhibitor, BB-94.


METHODS
The effect of BB-94 on the intrinsic invasive potential of matrilysin-transfected Du-145 cells was evaluated by an in vitro invasion assay. In addition a diaphragm invasion model, which provides an easily oriented structure in which the earliest penetration of the basal lamina can be observed, was used to investigate the effect of BB-94 on the invasion and growth of tumors formed by these cells when injected into S.C.I.D. mice.


RESULTS
The synthetic matrix metalloproteinase inhibitor, BB-94, was shown to effectively inhibit the invasion of matrigel and murine diaphragm.


CONCLUSIONS
Metalloproteinase inhibitors, such as BB-94, that are able to limit tumor growth, and local invasion, may decrease the invasion of invasive carcinomas.
Knox
J D
JD
Department of Pharmacology, McGill University, Montreal, Quebec, Canada. dknox@pharma.mcgill.ca
Bretton
L
L
Lynch
T
T
Bowden
G T
GT
Nagle
R B
RB
D000230:Adenocarcinoma / Q000473:pathology*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002278:Carcinoma in Situ / Q000188:drug therapy; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D051379:Mice; D016513:Mice, SCID; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D011480:Protease Inhibitors / Q000627:therapeutic use*; D013876:Thiophenes / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011480:Protease Inhibitors; D013876:Thiophenes; D010649:Phenylalanine; C080985:batimastat; D008666:Metalloendopeptidases