Expression of receptors for gut peptides in human pancreatic adenocarcinoma and tumour-free pancreas

Abstract

Summary Gut hormones that modulate the growth of normal pancreas may also modulate the growth of cancers originating from pancreas.This study visualized and compared the receptors for cholecystokinin (CCK), bombesin (BBS), secretin and vasoactive intestinal peptide (VIP) in tumour-free tissue sections of human pancreas (n =10) and pancreatic ductal adenocarcinomas (n =12) with storage phosphor autoradiography using radioligands. CCK-B receptors, present Several studies have focused on the effects of peptides or the status of peptide receptors on the pancreas of animal models. Rats treated with azaserine (inducing the acinar cell tumour) and hamsters treated with BOP [N-nitrosobis(2-oxopropyl)amine; inducing the ductal cell neoplasm] are the most frequently used experimental models to study pancreatic carcinogenesis (Longnecker et al, 1993). Promotive effects of cholecystokinin (CCK) on the growth of pancreatic neoplasms and overexpression of CCK receptors in pancreatic neoplastic lesions of azaserinetreated rats have been reported by studies from our and other groups (Douglas et al, 1989;Bell et al, 1992; Tang et al, 1995a). In the BOP-hamster model, however, the effects of CCK on pancreatic carcinogenesis are rather inconsistent (Johnson et al, 1983;Howatson et al, 1985;Meijers et al, 1990). In addition, the effects of other peptides, such as bombesin (BBS), secretin and vasoactive intestinal peptide (VIP), on the growth of pancreatic cancer in animal models are inconsistent and unclear (Townsend et al, 1981;Poston et al, 1988;Edwards et al, 1989;Meijers et al, 1991Meijers et al, , 1992. In the animal models, receptors for BBS, secretin and VIP disappear with the progress of pancreatic carcinogenesis (Tang et

Secretin receptors in the human liver: Expression in biliary tract and cholangiocarcinoma, but not in hepatocytes or hepatocellular carcinoma

“…The cholangiocarcinoma is an additional human malignancy, apart from pancreatic carcinomas and gastrinomas [8,11,12], in which secretin receptors have been shown to be expressed. In cholangiocarcinomas, secretin receptors were often heterogeneously expressed, which was significantly more frequently observed in grade 3 than in grade 2 carcinomas.…”

“…It is mainly responsible for the bicarbonate and water secretion from the pancreas [9] and for the gastrin release from the antral and duodenal mucosa [10]. Recently, it was recognized that secretin receptors are also expressed in the neoplastic counterparts of these tissues: they were found in pancreatic duct cancers and in pancreatic gastrinomas [8,11,12]. Analogous to somatostatin receptors, the secretin receptors in neoplasia are of potential use for in vivo tumor targeting.…”

Primary Culture of Pancreatic (Human) Acinar Cells

“…Despite considerable efforts in understanding pathophysiology of pancreatitis, the mechanism involved in development and course of this disease remains obscure. To study such mechanisms, a number of animal models exhibiting pancreatitis have been developed; however, the studies have indicated differential expression of receptors for various gut peptides in pancreatic acinar cells of humans as compared to those of rodents and pigs [2,3]. Under such conditions, pancreatic acinar cells may represent an experimental model system to study the mechanism of pathogenesis of pancreatitis in the research laboratory in the absence of suitable cell lines to authentically reproduce the physiological and pathophysiological function of the cells.…”

Bombesin Receptors in Distinct Tissue Compartments of Human Pancreatic Diseases

“…In the human pancreas, bombesin-like immunoreactivity has been localized by immunohistochemistry to nerve fibers innervating pancreatic acini, capillaries, ducts, and islets (Shimosegawa et al, 1993). Bombesin receptors have been identified with binding techniques under various experimental conditions in rat, guinea pig, and human pancreas tissues (Hajri et al, 1996;Huang et al, 1990;Jensen et al, 1978;Tang et al, 1997) indicative of a possible functional role of bombesin-like peptides in this organ (Deschodt-Lanckman et al, 1976). Information on the exact localization and distribution of bombesin receptors and their subtypes in the diseased human pancreas is, however, very limited.…”