Variable effect of streptozotocin-diabetes on the growth of hamster pancreatic cancer (H2T) in the Syrian hamster and nude mouse.
BACKGROUND
Streptozotocin-diabetes prevents induction of pancreatic tumors in several animal models and inhibits the growth of established human pancreatic cancer implants in nude mice. However, it also promotes growth of the hamster pancreatic cancer cell line, H2T, in the Syrian hamster. To test the hypothesis that these contradictory effects are due to tumor host differences, the growth of the H2T cell line was examined in the streptozotocin-diabetic nude mouse.


METHODS
H2T cells were implanted subcutaneously into streptozotocin-diabetic nude mice (n = 10) and untreated control mice (n = 10). After 21 days, tumors were excised and weighed. Plasma insulin and somatostatin were determined by radioimmunoassay.


RESULTS
After 3 weeks, tumors in the control group weighed 118 mg and tumors in the diabetic group weighed 28 mg (p < 0.001). Plasma insulin was significantly decreased in the streptozotocin-treated animals compared with control animals (insulin, 23 microU/ml vs 31 microU/ml; p < 0.001). In contrast, somatostatin was significantly elevated in the streptozotocin-diabetic group compared with the control group (somatostatin, 179 pg/ml versus 54 pg/ml, p < 0.001). Competitive binding studies revealed specific cell surface receptors for insulin (Kd, 15.5 nmol/L), and somatostatin (Kd, 2.5 nmol/L) on the H2T cells. In an in vitro cell proliferation assay, cell division was promoted by insulin (p < 0.01, maximum +11%) and inhibited by somatostatin (p < 0.01, maximum -18%).


CONCLUSIONS
The variable effect of streptozotocin-diabetes on pancreatic cancer growth is due to differences in the tumor host. The growth of pancreatic cancer, particularly in streptozotocin-diabetic nude mice, may be influenced by gut peptides in a receptor-dependent fashion.
Fisher
W E
WE
Department of Surgery, Ohio State University, Columbus 43210, USA.
Muscarella
P
P
Boros
L G
LG
Schirmer
W J
WJ
D000818:Animals; D001835:Body Weight; D006224:Cricetinae; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D008647:Mesocricetus; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000150:complications / Q000473:pathology*; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D018027:Receptors, Glucagon / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000378:metabolism; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D018027:Receptors, Glucagon; D017481:Receptors, Somatostatin; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin