Presence of membrane binding sites for [D-TRP6]-luteinizing hormone-releasing hormone in experimental pancreatic cancer.
Characteristics of binding sites (dissociation constant: Kd and maximal binding capacity: Bmax) for [D-Trp6]-luteinizing hormone-releasing hormone [( D-Trp6]-LH-RH]), somatostatin (SS-14) and epidermal growth factor (EGF) were evaluated in membrane fractions of N-Nitrosobis (2-oxopropyl) amine (BOP)-induced pancreatic adenocarcinoma of hamsters. Intact, normal hamster pancreata did not show any binding sites for [D-Trp6]-LH-RH, but specific [D-Trp6]-LH-RH binding sites with low affinity and high capacity were found after pancreatic cancer was induced with BOP. Membrane binding sites for SS-14 and EGF, with high affinity and low capacity were present, both in normal and cancerous pancreata. Normal hamster pancreatic tissue had significantly higher levels of SS-14 binding sites and lower concentration of EGF binding sites as compared to pancreatic carcinoma. In vivo treatment of hamsters bearing pancreatic cancers with microcapsules of agonist [D-Trp6]-LH-RH and the somatostatin analog RC-160 alone, or in combination, caused histopathological regression of tumors and concomitantly decreased the Kd and Bmax of [D-Trp6]-LH-RH, and increased the Bmax of the SS-14 binding sites. These findings represent the first demonstration of binding sites for [D-Trp6]-LH-RH in pancreatic cancers. Our results also suggest that tumor inhibitory effects of [D-Trp6]-LH-RH and RC-160 in pancreatic cancer could be mediated not only indirectly through suppression of sex-steroids, gastrointestinal hormones and growth factors, but also directly by an action on specific binding sites located on the tumor membranes.
Fekete
M
M
Endocrine, Polypeptide and Cancer Institute, Veterans Administration Medical Center, New Orleans, LA.
Zalatnai
A
A
Schally
A V
AV
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D006224:Cricetinae; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D008647:Mesocricetus; D009602:Nitrosamines; D010190:Pancreatic Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D011966:Receptors, LHRH / Q000378:metabolism*; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D017481:Receptors, Somatostatin; D013004:Somatostatin / Q000031:analogs & derivatives / Q000627:therapeutic use; D017329:Triptorelin Pamoate
D000970:Antineoplastic Agents; D009602:Nitrosamines; D011966:Receptors, LHRH; D017981:Receptors, Neurotransmitter; D017481:Receptors, Somatostatin; D017329:Triptorelin Pamoate; C051458:vapreotide; D007987:Gonadotropin-Releasing Hormone; D013004:Somatostatin; C013622:nitrosobis(2-oxopropyl)amine; D066246:ErbB Receptors