Pancreatic secretory trypsin inhibitor stimulates the growth of rat pancreatic carcinoma cells.
Pancreatic secretory trypsin inhibitor was examined for growth-promoting activity on five cell lines using standard cell culture techniques. One cell line, AR4-2J, derived from a rat pancreatic acinar cell carcinoma, responded with significantly increased incorporation of [3H]thymidine and colony formation. Pancreatic secretory trypsin inhibitor stimulated the incorporation of [3H]thymidine in liquid culture; the maximal increase was 61 +/- 10% above control (P less than 0.001) and was seen at a concentration of 10(-9) mol/L. Using a soft agarose clonogenic assay, pancreatic secretory trypsin inhibitor also consistently stimulated (3 assays) colony formation: the peak activity occurred at a concentration of 10(-10) mol/L which caused a 150 +/- 55% (mean +/- SE, P less than 0.05) increase above control. Aprotinin had no effect on the growth of AR4-2J cells and pancreatic secretory trypsin inhibitor did not bind to the epidermal growth factor receptor. AR4-2J cells were shown to produce pancreatic secretory trypsin inhibitor. The study raises the possibility that pancreatic secretory trypsin inhibitor provides autocrine stimulation of tumor cell growth.
Department of Medicine, Royal Postgraduate School of Medicine, Hammersmith Hospital, London, England.
T C
TC
Freeman
B J
BJ
Curry
J
J
Calam
J R
JR
Woodburn
D000818:Animals; D002277:Carcinoma / Q000473:pathology*; D003110:Colonic Neoplasms / Q000473:pathology; D005260:Female; D006801:Humans; D010190:Pancreatic Neoplasms / Q000473:pathology; D051381:Rats; D013274:Stomach Neoplasms / Q000473:pathology*; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014846:Vulvar Neoplasms / Q000473:pathology
D014359:Trypsin Inhibitor, Kazal Pancreatic