Growth effects of regulatory peptides on human pancreatic cancer lines PANC-1 and MIA PaCa-2

Summary The in vivo administration of somatostatin (SS) or its analogues is capable of suppressing the growth of pancreatic cancer in experimental animals. We examined the effects of SS-14 and its analogue RC-160 on the in vitro growth of two human pancreatic cancer cell lines MiaPaCa-2 and Panc-1 stimulated with epidermal growth factor (EGF) or insulin-like growth factor 1 (IGF-1). Neither SS-14 nor RC-160 inhibited the growth of either cell line. In contrast RC-160 did inhibit the EGF-stimulated growth of a rat pancreatic cancer cell line AR42J. Binding studies with '251-Tyr" somatostatin revealed the presence of a single class of high affinity binding sites with a Kd of 0.20 ± 0.05 nM and a B.,,, of 2.1 + 0.26 pmoles mg-' protein on AR42J but no displaceable binding was observed on MiaPaCa-2 or Panc-1. We conclude that lack of receptors accounts for the failure of SS-14 and RC-160 to influence the growth of human pancreatic cancer in vitro. These results, taken together with other findings, lead us to question the therapeutic efficacy of somatostatin and its analogues as mono-therapy in the treatment of human pancreatic cancer.

Section: Cellmentioning

confidence: 69%

Human pancreatic cancer cell lines do not express receptors for somatostatin

Gillespie

Poston²,

Schächter³

et al. 1992

“…The role of BBS on pancreatic cancer cell lines is controversial Liehr et al, 1990;Qin et al, 1994). The comparison of BBS receptors between tumour-free pancreas and pancreatic cancer in the present study does not favour a direct action of BBS on the growth of pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

“…However, less than half of the pancreatic cancers in this study expressed secretin receptors. These variable changes in the status of secretin receptors may help in the understanding of why one group showed no effect of secretin on cell proliferation of pancreatic cancer (Liehr et al, 1990), whereas another group identified secretin receptors in human pancreatic cancer (Estival et al, 1981).…”

Section: Discussionmentioning

confidence: 99%

“…So far, the growth effects of regulatory peptides and the expression of peptide receptors on human pancreatic cancer cell lines are still controversial (Estival et al, 1983;Alexander et al, 1988;Poston et al, 1988;Liehr et al, 1990;Smith et al, 1991;Qin et al, 1994 cancer was used for histological examination, while the other part was rapidly frozen at -80°C. All specimens of the tumours were of well-differentiated ductal pancreatic cancers.…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

Tang

Biemond²,

Offerhaus

et al. 1997

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

“…These cell lines have already been described in detail (Kyriazis et al, 1982;Liehr et al, 1990;Mai et al, 1990;Haberern-Blood et al, 1987;Kloppel et al, 1985). The PaCa-2 and PaCa-3 cell lines were established from the corresponding nude mouse tumours (see below).…”

Section: Methodsmentioning

confidence: 99%

Human ductal adenocarcinomas of the pancreas express extracellular matrix proteins

Löhr

Trautmann²,

Göttler³

et al. 1994

Summary Pancreatic ductal adenocarcinomas are characterised by a dense connective tissue reaction. To test the hypothesis that stroma components are synthesised and produced by the tumour cells themselves, eight cell lines as well as six xenografted tumours from human ductal adenocarcinomas of the pancreas were examined for the expression of extracellular matrix proteins (ECM), using cDNA probes and antibodies to collagen types I, III and IV, vitronectin, fibronectin, undulin and laminin. All tumour cell lines (CAPAN-1, CAPAN-2, AsPC-1, BxPC-3, PANC-1, PaCa-2, PaCa-3, PaCa-44) and xenografted human pancreatic tumours expressed at least one of the examined ECM at the RNA (collagen type IV> laminin = fibronectin = vitronectin> collagen type III> undulin> collagen type I) or protein level (collagen type IV = collagen type III> vitronectin> laminin> collagen type I = fibronectin> undulin). In nude mouse tumours expression of laminin and collagen I was most pronounced in well-differentiated carcinomas. In a few tumours, collagen type III, vitronectin and undulin were expressed on the luminal side of the neoplastic glands, suggesting loss of normal polar differentiation. Incubation with fetal calf serum modulated ECM RNA levels to a varying extent in all but one cell line (AsPC-1). The results suggest that human pancreatic ductal adenocarcinomas cells are capable of synthesising and producing extracellular matrix proteins in vitro and in vivo, but that the extent and pattern of ECM expression differs between the various tumours and conditions tested.