We have examined the
secretogogue responsiveness and the pattern of secretory
proteins produced by a transplantable rat pancreatic acinar cell
tumor. Dispersed
tumor cells were found to discharge secretory
proteins in vitro when incubated with
hormones that act on four different classes of receptors:
carbamylcholine,
caerulein,
secretin-
vasoactive intestinal peptide, and
bombesin. With all
hormones tested, maximal discharge from
tumor cells was only about one-half that of control pancreatic lobules, but occurred at the same dose optima except for
secretin, whose dose optimum was 10-fold higher. Biochemical analysis of secretory
proteins discharged by the
tumor cells was carried out by crossed immunoelectrophoresis and by two-dimensional isoelectric focusing-SDS
polyacrylamide gel electrophoresis. To establish a baseline for comparison, secretory
proteins from normal rat pancreas were identified according to enzymatic activity and correlated with migration position on two-dimensional
gels. Our results indicate that a group of basic
polypeptides including
proelastase, basic
trypsinogen, basic
chymotrypsinogen, and
ribonuclease, two out of three forms of
procarboxypeptidase B, and the major
lipase species were greatly reduced or absent in
tumor cell secretion. In contrast, the amount of acidic
chymotrypsinogen was notably increased compared with normal acinar cells. Although the acinar
tumor cells are highly differentiated cytologically and express functional receptors for several classes of pancreatic
secretagogues, they show quantitative and qualitative differences when compared with normal pancreas with regard to their production of secretory
proteins.