In vivo inhibition of cysteine proteinases delays the onset of growth of human pancreatic cancer explants

An animal model was used to study the effects of oral treatment with a smal l molecular selective inhibitor of cysteine proteinases, Z-Phe-Arg-fluorome thylketone (Z-Phe-Arg-FMK) on primary tumour development. Poorly differenti ated rapidly growing and moderately differentiated slowly growing human pan creatic tumours were implanted in the neck of nude mice that were orally tr eated or not with the inhibitor. Growth rates of the tumours were determine d during 38 days after implantation. The poorly differentiated tumours were not affected by treatment with the inhibitor, Development of the moderatel y differentiated tumours was inhibited significantly by Z-Phe-Arg-FMK treat ment. Moreover, the amount of stroma was increased and the volume of cancer cells was reduced in the moderately differentiated tumours that had grown in the treated animals, Reduction in size of the tumours was not achieved b y reduction in growth rate but in a delay of the onset of growth, It is con cluded that cysteine proteinases play a transient role at the start of tumo ur development only when cancer cells are surrounded by stroma as was the c ase in the moderately differentiated but not in the poorly differentiated p ancreatic tumours. However, this role of cysteine proteinases can easily be taken over by other proteinases. (C) 2000 Cancer Research Campaign.