Expression of the somatostatin receptor subtype-2 gene predicts response of human pancreatic cancer to octreotide

W. E. Fisher, Peter Muscarella, T. M. O'Dorisio, M. S. O'Dorisio, J. A. Kim, T. A. Doran, C. L. Sabourin, W. J. Schirmer

Research output: Contribution to journalArticle

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Abstract

Background. Somatostatin inhibits proliferation of many solid tumors. The current study examines whether inhibition of the growth of pancreatic cancer by the somatostatin analog, octreotide, requires tumor expression of somatostatin receptors. Methods. We studied five human pancreatic cancer cell lines, Capan-1, Capan-2, CAV, MIA PaCa-2, and Panc-1. Solid tumors were established in nude mice (n = 20/cell line) by flank injection of tumor cells. Subcutaneous octreotide (500 μg/kg/day) was administered by osmotic pumps to 10 of the animals in each group, and the other 10 received control infusions of saline solution. On day 36, the tumors were excised and weighed. Plasma levels of the putative trophic peptides cholecystokinin, epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), and insulin were assessed by radioimmunoassay. Each of the five cell lines was assayed for the presence of cell surface somatostatin receptors by using whole cell competitive binding assays with 125I-somatostatin. Expression of the somatostatin receptor subtype-2 (SSR2) gene was determined with reverse transcriptase-polymerase chain reactions. Southern blot hybridization was used to assess the presence of the SSR2 gene. Results. Octreotide inhibited tumor growth in the MIA PaCa-2 group (512 ± 75 mg control versus 285 ± 71 mg treated; p < 0.05) but had no significant effect on tumor weight in the other four cell lines. Plasma levels of cholecystokinin, epidermal growth factor, insulin-like growth factor-1, and insulin were not altered by chronic octreotide infusion. Cell surface somatostatin receptors and SSR2 gene expression were detected only in the MIA PaCa-2 tumors. The gene for the SSR2 receptor was found in all five tumor lines. Couclusions. Octreotide-mediated inhibition of pancreatic cancer growth is dependent on expression of somatostatin receptors. The expression of somatostatin receptors should be considered in the design and interpretation of clinical trials with somatostatin analogs for treatment of pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)234-241
Number of pages8
JournalSurgery
Volume120
Issue number2
StatePublished - 1996
Externally publishedYes

Fingerprint

Octreotide
Pancreatic Neoplasms
Somatostatin Receptors
Somatostatin
Genes
Neoplasms
Cell Line
Cholecystokinin
Cell Surface Receptors
Somatomedins
Epidermal Growth Factor
Growth
Insulin
Competitive Binding
somatostatin receptor 2
Southern Blotting
Tumor Burden
Reverse Transcriptase Polymerase Chain Reaction
Nude Mice
Sodium Chloride

ASJC Scopus subject areas

  • Surgery

Cite this

Fisher, W. E., Muscarella, P., O'Dorisio, T. M., O'Dorisio, M. S., Kim, J. A., Doran, T. A., ... Schirmer, W. J. (1996). Expression of the somatostatin receptor subtype-2 gene predicts response of human pancreatic cancer to octreotide. Surgery, 120(2), 234-241.

Expression of the somatostatin receptor subtype-2 gene predicts response of human pancreatic cancer to octreotide. / Fisher, W. E.; Muscarella, Peter; O'Dorisio, T. M.; O'Dorisio, M. S.; Kim, J. A.; Doran, T. A.; Sabourin, C. L.; Schirmer, W. J.

In: Surgery, Vol. 120, No. 2, 1996, p. 234-241.

Research output: Contribution to journalArticle

Fisher, WE, Muscarella, P, O'Dorisio, TM, O'Dorisio, MS, Kim, JA, Doran, TA, Sabourin, CL & Schirmer, WJ 1996, 'Expression of the somatostatin receptor subtype-2 gene predicts response of human pancreatic cancer to octreotide', Surgery, vol. 120, no. 2, pp. 234-241.
Fisher, W. E. ; Muscarella, Peter ; O'Dorisio, T. M. ; O'Dorisio, M. S. ; Kim, J. A. ; Doran, T. A. ; Sabourin, C. L. ; Schirmer, W. J. / Expression of the somatostatin receptor subtype-2 gene predicts response of human pancreatic cancer to octreotide. In: Surgery. 1996 ; Vol. 120, No. 2. pp. 234-241.
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abstract = "Background. Somatostatin inhibits proliferation of many solid tumors. The current study examines whether inhibition of the growth of pancreatic cancer by the somatostatin analog, octreotide, requires tumor expression of somatostatin receptors. Methods. We studied five human pancreatic cancer cell lines, Capan-1, Capan-2, CAV, MIA PaCa-2, and Panc-1. Solid tumors were established in nude mice (n = 20/cell line) by flank injection of tumor cells. Subcutaneous octreotide (500 μg/kg/day) was administered by osmotic pumps to 10 of the animals in each group, and the other 10 received control infusions of saline solution. On day 36, the tumors were excised and weighed. Plasma levels of the putative trophic peptides cholecystokinin, epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), and insulin were assessed by radioimmunoassay. Each of the five cell lines was assayed for the presence of cell surface somatostatin receptors by using whole cell competitive binding assays with 125I-somatostatin. Expression of the somatostatin receptor subtype-2 (SSR2) gene was determined with reverse transcriptase-polymerase chain reactions. Southern blot hybridization was used to assess the presence of the SSR2 gene. Results. Octreotide inhibited tumor growth in the MIA PaCa-2 group (512 ± 75 mg control versus 285 ± 71 mg treated; p < 0.05) but had no significant effect on tumor weight in the other four cell lines. Plasma levels of cholecystokinin, epidermal growth factor, insulin-like growth factor-1, and insulin were not altered by chronic octreotide infusion. Cell surface somatostatin receptors and SSR2 gene expression were detected only in the MIA PaCa-2 tumors. The gene for the SSR2 receptor was found in all five tumor lines. Couclusions. Octreotide-mediated inhibition of pancreatic cancer growth is dependent on expression of somatostatin receptors. The expression of somatostatin receptors should be considered in the design and interpretation of clinical trials with somatostatin analogs for treatment of pancreatic cancer.",
author = "Fisher, {W. E.} and Peter Muscarella and O'Dorisio, {T. M.} and O'Dorisio, {M. S.} and Kim, {J. A.} and Doran, {T. A.} and Sabourin, {C. L.} and Schirmer, {W. J.}",
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T1 - Expression of the somatostatin receptor subtype-2 gene predicts response of human pancreatic cancer to octreotide

AU - Fisher, W. E.

AU - Muscarella, Peter

AU - O'Dorisio, T. M.

AU - O'Dorisio, M. S.

AU - Kim, J. A.

AU - Doran, T. A.

AU - Sabourin, C. L.

AU - Schirmer, W. J.

PY - 1996

Y1 - 1996

N2 - Background. Somatostatin inhibits proliferation of many solid tumors. The current study examines whether inhibition of the growth of pancreatic cancer by the somatostatin analog, octreotide, requires tumor expression of somatostatin receptors. Methods. We studied five human pancreatic cancer cell lines, Capan-1, Capan-2, CAV, MIA PaCa-2, and Panc-1. Solid tumors were established in nude mice (n = 20/cell line) by flank injection of tumor cells. Subcutaneous octreotide (500 μg/kg/day) was administered by osmotic pumps to 10 of the animals in each group, and the other 10 received control infusions of saline solution. On day 36, the tumors were excised and weighed. Plasma levels of the putative trophic peptides cholecystokinin, epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), and insulin were assessed by radioimmunoassay. Each of the five cell lines was assayed for the presence of cell surface somatostatin receptors by using whole cell competitive binding assays with 125I-somatostatin. Expression of the somatostatin receptor subtype-2 (SSR2) gene was determined with reverse transcriptase-polymerase chain reactions. Southern blot hybridization was used to assess the presence of the SSR2 gene. Results. Octreotide inhibited tumor growth in the MIA PaCa-2 group (512 ± 75 mg control versus 285 ± 71 mg treated; p < 0.05) but had no significant effect on tumor weight in the other four cell lines. Plasma levels of cholecystokinin, epidermal growth factor, insulin-like growth factor-1, and insulin were not altered by chronic octreotide infusion. Cell surface somatostatin receptors and SSR2 gene expression were detected only in the MIA PaCa-2 tumors. The gene for the SSR2 receptor was found in all five tumor lines. Couclusions. Octreotide-mediated inhibition of pancreatic cancer growth is dependent on expression of somatostatin receptors. The expression of somatostatin receptors should be considered in the design and interpretation of clinical trials with somatostatin analogs for treatment of pancreatic cancer.

AB - Background. Somatostatin inhibits proliferation of many solid tumors. The current study examines whether inhibition of the growth of pancreatic cancer by the somatostatin analog, octreotide, requires tumor expression of somatostatin receptors. Methods. We studied five human pancreatic cancer cell lines, Capan-1, Capan-2, CAV, MIA PaCa-2, and Panc-1. Solid tumors were established in nude mice (n = 20/cell line) by flank injection of tumor cells. Subcutaneous octreotide (500 μg/kg/day) was administered by osmotic pumps to 10 of the animals in each group, and the other 10 received control infusions of saline solution. On day 36, the tumors were excised and weighed. Plasma levels of the putative trophic peptides cholecystokinin, epidermal growth factor (EGF), insulin-like growth factor-1 (IGF-1), and insulin were assessed by radioimmunoassay. Each of the five cell lines was assayed for the presence of cell surface somatostatin receptors by using whole cell competitive binding assays with 125I-somatostatin. Expression of the somatostatin receptor subtype-2 (SSR2) gene was determined with reverse transcriptase-polymerase chain reactions. Southern blot hybridization was used to assess the presence of the SSR2 gene. Results. Octreotide inhibited tumor growth in the MIA PaCa-2 group (512 ± 75 mg control versus 285 ± 71 mg treated; p < 0.05) but had no significant effect on tumor weight in the other four cell lines. Plasma levels of cholecystokinin, epidermal growth factor, insulin-like growth factor-1, and insulin were not altered by chronic octreotide infusion. Cell surface somatostatin receptors and SSR2 gene expression were detected only in the MIA PaCa-2 tumors. The gene for the SSR2 receptor was found in all five tumor lines. Couclusions. Octreotide-mediated inhibition of pancreatic cancer growth is dependent on expression of somatostatin receptors. The expression of somatostatin receptors should be considered in the design and interpretation of clinical trials with somatostatin analogs for treatment of pancreatic cancer.

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