Tumor Cell-Induced Platelet Aggregation in Vitro by Human Pancreatic Cancer Cell Lines

1995 ◽  
Vol 30 (10) ◽  
pp. 1008-1016 ◽  
Author(s):  
E. Heinmöller ◽  
T. Schropp ◽  
O. Kisker ◽  
B. Simon ◽  
R. Seitz ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Platelet Aggregation ◽  
Tumor Cell ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Pancreatic Cancer ◽  
Human Pancreatic Cancer Cell

Identification and characterization of CCK-B/gastrin receptors in human pancreatic cancer cell lines

1994 ◽  
Vol 266 (1) ◽  
pp. R277-R283 ◽  
Author(s):  
J. P. Smith ◽  
G. Liu ◽  
V. Soundararajan ◽  
P. J. McLaughlin ◽  
I. S. Zagon
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Pancreatic Cancer ◽  
Human Pancreatic Cancer Cell ◽  
Pancreatic Cancer Cells

The gastrointestinal peptide cholecystokinin (CCK) is known to stimulate growth of human pancreatic cancer in a receptor-mediated fashion. The purpose of this study was to characterize the receptor responsible for the trophic effects of CCK in cancer cells. With the use of homogenates of PANC-1 human pancreatic cancer cells grown in vitro, the binding characteristics and optimal conditions of radiolabeled selective CCK-receptor antagonists ([3H]L-365,260 and [3H]L-364,718) were examined. Specific and saturable binding was detected with [3H]L-365,260, and Scatchard analysis revealed that the data were consistent for a single site of binding with a binding affinity of 4.3 +/- 0.6 nM and a binding capacity (Bmax) of 283 +/- 68 fmol/mg protein in log phase cells. Binding was dependent on protein concentration, time, temperature, and pH and was sensitive to Na+, K+, Mg2+, and ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. In contrast to log phase cells, Bmax decreased by 80 and 92% in confluent and postconfluent cultures, respectively. Subcellular fractionation studies revealed that binding was in the membrane fraction. Competition experiments indicated that L-365,260 and gastrin were more effective at displacing the radiolabeled L-365,260 than CCK. No binding was detected with the CCK-A antagonist [3H]L-364,718. Assays performed with [3H]L-365,260 on five additional human pancreatic cancer cell lines in vitro and tumor tissue from xenografts in nude mice also revealed specific and saturable binding. These results provide the first identification of a CCK-B/gastrin receptor in human pancreatic cancer cells and tumors and explain the effects of CCK on the growth of this malignancy.

In vitro chemosensitivity of human pancreatic cancer cell lines

1996 ◽  
Vol 20 (3) ◽  
pp. 185-190 ◽  
Author(s):  
Yasunori Sawabe ◽  
Hisakazu Yamagishi ◽  
Nozomi Yamaguchi ◽  
Yoshiro Yamamura ◽  
Takahiro Oka
Keyword(s):  
Pancreatic Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Pancreatic Cancer ◽  
Human Pancreatic Cancer Cell ◽  
In Vitro Chemosensitivity

Effect of apricoxib, a novel COX-2 inhibitor, on the efficacy of standard therapy in human pancreatic cancer cell lines in vitro and in vivo.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 227-227
Author(s):  
A. R. Kirane
Keyword(s):  
Pancreatic Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Pancreatic Cancer ◽  
Human Pancreatic Cancer Cell ◽  
Cox 2

227 Background: Gemcitabine-erlotinib is standard of care (SOC) for pancreatic cancer, but this regimen can still be improved upon with regard to prolonging patient survival. Cyclo-oxygenase-2 (COX-2) is overexpressed in pancreatic cancer and implicated in pancreatic tumor progression. Inhibition of COX-2 decreases tumor growth, augments the activity of both gemcitabine and EGFR inhibition, and may play a role in preventing or reversing EMT. This study characterized the effects of COX-2 inhibition on pancreatic cancer cell lines and determined if the addition of apricoxib enhances sensitivity to chemotherapy. Methods: Baseline EGFR and COX-2 expression were determined in 7 human pancreatic cancer cell lines and functional responses measured by changes in phospho-EGFR (p-EGFR) and prostaglandin E2 (PGE2) production by ELISA. Cytotoxicity was determined for gemcitabine, erlotinib, and apricoxib independently and in combination by MTS assay. The effect of SOC therapy alone or in combination with 10 or 30 mg/kg apricoxib PO on AsPC-1 and Colo357 tumors in vivo was determined in SCID mice bearing established orthotopic xenografts. Tissue was analyzed by IHC and VEGF levels were determined by ELISA. Results: All lines expressed EGFR and COX-2, but expression alone was not predictive of p-EGFR level, PGE2 production, or response to drug therapy. In vitro, AsPC-1 cells had negligible COX-2 activity, whereas Colo357 cells displayed high levels of COX-2 and PGE2 production. Cell growth and COX-2 activity decreased in all cell lines in the presence of apricoxib and addition of apricoxib improved response to chemotherapy. In vivo, addition of apricoxib to SOC significantly reduced primary tumor growth and almost eradicated metastases in mice bearing Colo357 but not AsPC-1 xenografts. Plasma VEGF levels were unaltered by apricoxib treatment in AsPC-1-bearing animals but were suppressed to undetectable levels in Colo357-bearing animals. Markers of EMT were significantly decreased in animals treated with apricoxib. Conclusions: Apricoxib enhances the efficacy of gemcitabine and erlotinib in vitro and in vivo and warrants clinical evaluation in patients with pancreatic cancer. A phase II study is ongoing. No significant financial relationships to disclose.

Gastrin regulates growth of human pancreatic cancer in a tonic and autocrine fashion

1996 ◽  
Vol 270 (5) ◽  
pp. R1078-R1084 ◽  
Author(s):  
J. P. Smith ◽  
A. Shih ◽  
Y. Wu ◽  
P. J. McLaughlin ◽  
I. S. Zagon
Keyword(s):  
Gene Expression ◽  
Pancreatic Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Pancreatic Cancer Cell ◽  
Cancer Cell Lines ◽  
Human Pancreatic Cancer ◽  
Growth Media ◽  
Human Pancreatic Cancer Cell ◽  
Cell Extracts

The gastrointestinal peptides gastrin and cholecystokinin (CCK) stimulate growth of human pancreatic cancer through a CCK-B/gastrin- like receptor. In the present study we evaluated whether growth of human pancreatic cancer is endogenously regulated by gastrin. Immunohistomical examination of BxPC-3 cells and tumor xenografts revealed specifc gastrin immunoreactivity. Gastrin was detected by radioimmunoassay in pancreatic cancer cell extracts and in pancreatic cancer cell extracts and in the growth media. With use of reverse-transcriptase polymerase chain reaction gastrin gene expression was detected in both cultured BxPC-3 cancer cells and transplanted tumors, as well as seven addition human pancreatic cancer cell lines. Growth of BxPC-3 human pancreatic cancer cell in serum-free medium was inhibited by the addition of the CCK-B/gastrin receptor antagonist L-365,260, and gastrin treatment reversed the inhibitory effect of the antagonist. A selective gastrin antibody (Ab repressed growth of BxPC-3 cells. Gastrin immunoreactivity was detected in fresh human pancreatic cancer specimens but not in normal human pancreatic tissue. These data provide the first evidence that growth of a human pancreatic cancer is tonically stimulated by the autocrine production of gastrin. Evidence for the ubiquity of this system was provided by the detection of gastrin gene expression in multiple human pancreatic cancer cell lines and detection of gastrin in cell lines and fresh pancreatic tumors.

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