Membrane receptors for peptides in experimental and human pancreatic cancers.
Membrane receptors for [D-Trp6]-luteinizing hormone-releasing hormone [( D-Trp6]-LH-RH), somatostatin (SS-14), and epidermal growth factor (EGF) were investigated in experimental N-nitrosobis-(2-oxopropyl)-amine (BOP)-induced pancreatic cancers of hamsters and in specimens of normal human pancreas and human pancreatic cancer obtained from autopsies. Membrane receptors for [D-Trp6]-LH-RH were absent in the pancreas of normal hamsters, but appeared after the carcinoma was induced with BOP. Binding capacity of SS-14 receptors was lower in membranes of BOP-induced pancreatic cancers than in the normal pancreas. In the BOP-induced pancreatic cancers, the receptors were also characterized following in vivo treatment of hamsters with microcapsules of the agonist [D-Trp6]-LH-RH, somatostatin analog RC-160, and the combination of both peptides, which resulted in significant tumor inhibition. Therapy with [D-Trp6]-LH-RH and RC-160, alone or in combination, decreased the binding capacity of receptors for [D-Trp6]-LH-RH, but increased Bmax for SS-14. There were no significant changes in characteristics of the EGF receptor following these therapies. Membranes from human pancreatic cancers showed binding sites for [D-Trp6]-LH-RH, but no binding was detected in normal human pancreas. The presence of receptors for LH-RH in pancreatic tumors of hamster and humans raises the intriguing possibility that LH-RH could be involved in complex interactions that contribute to the appearance of pancreatic cancer. The binding capacity of receptors for SS-14 in human pancreatic cancer membranes was lower, while Bmax for EGF was higher, as compared to normal pancreas.(ABSTRACT TRUNCATED AT 250 WORDS)
Fekete
M
M
Endocrine, Polypeptide and Cancer Institute, Veterans Administration Medical Center, New Orleans, Louisiana 70146.
Zalatnai
A
A
Comaru-Schally
A M
AM
Schally
A V
AV
D000230:Adenocarcinoma / Q000032:analysis / Q000139:chemically induced / Q000473:pathology / Q000648:ultrastructure*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology; D001344:Autopsy; D002273:Carcinogens / Q000494:pharmacology; D006224:Cricetinae; D066246:ErbB Receptors / Q000032:analysis*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007986:Luteinizing Hormone / Q000494:pharmacology; D008647:Mesocricetus; D009602:Nitrosamines / Q000009:adverse effects; D010190:Pancreatic Neoplasms / Q000032:analysis / Q000139:chemically induced / Q000473:pathology / Q000648:ultrastructure*; D011966:Receptors, LHRH / Q000032:analysis*; D011986:Receptors, Somatotropin / Q000032:analysis*; D013004:Somatostatin / Q000494:pharmacology / Q000031:analogs & derivatives; D017329:Triptorelin Pamoate
D000970:Antineoplastic Agents; D002273:Carcinogens; D009602:Nitrosamines; D011966:Receptors, LHRH; D011986:Receptors, Somatotropin; D017329:Triptorelin Pamoate; C051458:vapreotide; D007987:Gonadotropin-Releasing Hormone; D013004:Somatostatin; C013622:nitrosobis(2-oxopropyl)amine; D007986:Luteinizing Hormone; D066246:ErbB Receptors