Presence of membrane binding sites for [D-TRP⁶]-luteinizing hormone-releasing hormone in experimental pancreatic cancer

Characteristics of binding sites (dissociation constant: K_d and maximal binding capacity: B_max) 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 K_d and B_max of [D-Trp⁶]-LH-RH, and increased the B_max 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.