Cholecystokinin stimulates growth of human pancreatic adenocarcinoma SW-1990

Smith, Jill P.; Solomon, Travis E.; Bagheri, Saeed; Kramer, Scott

doi:10.1007/bf01536744

Cited by 89 publications

(53 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Of the 11 studies indicating a positive association, only four demonstrated an increased pancreatic cancer risk 5 or more years prior to the cancer diagnosis (Norell and Ahlbom, 1986;Hyvarinen and Partanen, 1987;Shibata et al, 1994;Chow et al, 1998), while our study is the first to show an increased risk for subjects with a cholecystectomy at least 20 years prior to the cancer diagnosis, an interval too long to be considered prodromal to pancreatic cancer. A causal relation is further supported by experimental studies showing that cholecystectomy increases circulating levels of cholecystokinin (CCK), which is a major regulator of pancreatic growth and enzyme secretion (Warshaw and Fernandez-del Castillo, 1992), and a promoter of pancreatic carcinogenesis in rodents (Howatson and Carter, 1985;Smith et al, 1990). Potential confounding by obesity, which is a risk factor for cholelithiasis and pancreatic cancer, was ruled out in our study.…”

Section: Discussionmentioning

confidence: 60%

Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer

et al. 1999

View full text Add to dashboard Cite

In a population-based case-control study of pancreatic cancer conducted in three areas of the USA, 484 cases and 2099 controls were interviewed to evaluate the aetiologic role of several medical conditions/interventions, including diabetes mellitus, cholecystectomy, ulcer/gastrectomy and allergic states. We also evaluated risk associated with family history of cancer. Our findings support previous studies indicating that diabetes is a risk factor for pancreatic cancer, as well as a possible complication of the tumour. A significant positive trend in risk with increasing years prior to diagnosis of pancreatic cancer was apparent ( P -value for test of trend = 0.016), with diabetics diagnosed at least 10 years prior to diagnosis having a significant 50% increased risk. Those treated with insulin had risks similar to those not treated with insulin (odds ratio (OR) = 1.6 and 1.5 respectively), and no trend in risk was associated with increasing duration of insulin treatment. Cholecystectomy also appeared to be a risk factor, as well as a consequence of the malignancy. Subjects with a cholecystectomy at least 20 years prior to the diagnosis of pancreatic cancer experienced a 70% increased risk, which was marginally significant. In contrast, subjects with a history of duodenal or gastric ulcer had little or no elevated risk (OR = 1.2; confidence interval = 0.9–1.6). Those treated by gastrectomy had the same risk as those not receiving surgery, providing little support for the hypothesis that gastrectomy is a risk factor for pancreatic cancer. A significant 40% reduced risk was associated with hay fever, a non-significant 50% decreased risk with allergies to animals, and a non-significant 40% reduced risk with allergies to dust/moulds. These associations, however, may be due to chance since no risk reductions were apparent for asthma or several other types of allergies. In addition, we observed significantly increased risks for subjects reporting a first-degree relative with cancers of the pancreas (OR = 3.2), colon (OR = 1.7) or ovary (OR = 5.3) and non-significantly increased risks for cancers of the endometrium (OR = 1.5) or breast (OR = 1.3). The pattern is consistent with the familial predisposition reported for pancreatic cancer and with the array of tumours associated with hereditary non-polyposis colon cancer. © 1999 Cancer Research Campaign

show abstract

Section: Discussionmentioning

confidence: 60%

Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer

et al. 1999

View full text Add to dashboard Cite

show abstract

“…The response in pancreatic AR4-2J tumour cells contrasts with that in the normal mouse pancreatic acinar cells in which the growth response to gastrin is reported to be mediated via the CCK-A receptor (Logsdon, 1987). Human pancreatic cancer cell growth is stimulated by CCK (Smith et al, 1990b;; the receptors mediating this response require evaluating. The sequence of events linking occupation of gastrin/CCK-B receptors to enhanced cell division has yet to be elucidated, but early events may include the activation of Na+/H+ exchange (Bastie et al, 1988) and ornithine decarboxylase (Scemama et al, 1989).…”

Section: Discussionmentioning

confidence: 91%

“…The trophic effects of gastrin on a transplantable murine colonic adenocarcinoma in vivo and on human gastric and colonic cancer xenografts in nude mice are well recognised (Singh et al, 1986;Winsett et al, 1986;Smith & Solomon, 1988;Watson et al, 1989). Similarly, the structurally-related cholecystokinin (CCK) has been reported to enhance pancreatic tumour formation in carcinogen-treated animals and growth of human pancreatic cancer xenografts in nude mice (Howatson & Carter, 1985;Smith et al, 1990b). Gastrin receptors are found on a large proportion of tumours from patients with colon cancers (Upp et al, 1989).…”

mentioning

confidence: 99%

Autocrine stimulation of growth of AR4-2J rat pancreatic tumour cells by gastrin

Blackmore

Bh²

1992

Br J Cancer

View full text Add to dashboard Cite

Summary The control of cell proliferation by gastrin has been investigated in a rat pancreatic tumour cell line, AR4-2J. Exogenous gastrin, 10-12 to 10-8 M, stimulated cell growth of thymidine-synchronised AR4-2J cells cultured over 48 h in serum-free medium. Cell lysates of AR4-2J cells contained an average of 4.5 and 3.5 pg gastrin per 106 cells, when grown in serum-supplemented or serum-free media, respectively, as revealed by radioimmunoassay. In serum-free medium, AR4-2J secrete 34ngl 10-6 cells of gastrin over 48h. Addition of an anti-gastrin immunoglobulin preparation, but not control immunoglobulins, caused a maximum 52% reduction in cell growth. These data are consistent with an autocrine role for gastrin in the control of AR4-2J cell growth. These results were supported by studies with gastrin/CCK receptor antagonists. Six non-peptide gastrin/CCK receptor antagonists inhibited AR4-2J cell growth in a concentration-related manner. The concentration required for 50% inhibition (IC50) of cell growth by the amino acid-derived antagonists proglumide (3.5 x 10-M), benzotript (1.8 x 10-3 M), loxiglumide (1.1 x 10-4 M) and lorglumide (6.7 x 10-5 M) were of the same order and significantly correlated with their IC50 for inhibition of 1251-gastrin binding to AR4-2J cells. Inhibition of cell growth by these antagonists was partially reversed by the addition of exogenous gastrin. In contrast, the ICm for inhibition of cell growth with two benzodiazepine-derived antagonists, the CCK-B receptor antagonist L-365,260 (4.6 x 10-5 M) and the CCK-A receptor antagonist devazepide (1.7 x 10-' M) were two-three orders of magnitude greater than those required to inhibit gastrin binding (10-8-10-7 M). The growth inhibitory effects of L-365,260 and devazepide were not reversed by exogenous gastrin suggesting these benzodiazepine-derived antagonists do not inhibit cell growth by interaction with gastrin receptors. The results are consistent with gastrin being an autocrine growth factor in AR4-2J cells, and that stimulation of cell growth is due to stimulation of the gastrin, rather than CCK-B, receptor sub-type. This study highlights that gastrin receptor antagonists warrant further investigation as agents to control growth of tumours, such as those from the gastrointestinal tract, which express gastrin receptors.

show abstract

“…However, stimulative, inhibitory or no effect of CCK on the growth of human pancreatic cancer cell lines or human pancreatic cancer xenografts in nude mice have been reported (Upp et al, 1987;Smith et al, 1990;Nio et al, 1993). Although the membrane fractions of some pancreatic cancer cell lines, such as MIA PaCa-2, BxPC-3, Capan-1, MDA-Amp-7 and MDA-Panc-28, expressed CCK-B receptors (Smith et al, 1994), no specific CCK binding was detected in the membranes of other pancreatic cancer cell lines (Singh et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

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

Tang

Biemond²,

Offerhaus

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

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

show abstract

Cholecystokinin stimulates growth of human pancreatic adenocarcinoma SW-1990

Cited by 89 publications

References 34 publications

Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer

Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer

Autocrine stimulation of growth of AR4-2J rat pancreatic tumour cells by gastrin

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

Contact Info

Product

Resources

About