TY - JOUR
T1 - Expression of the somatostatin receptor subtype-2 gene predicts response of human pancreatic cancer to octreotide
AU - Fisher, W. E.
AU - Muscarella, P.
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.
N1 - Funding Information:
SOMATOSTATIN HAS BEEN CHARACTERIZEDa s the universal off-switch because it inhibits the release of growth hormone and virtually all gastrointestinal hormones. Recent studies with experimental tumor models of pancreatic cancer have shown an antiproliferative effect of somatostatin both in vitro and in vivo. 1 These studies suggest that somatostatin and its analogs might serve as Supported by grants from The AmericanC ancer Society,T he Bremer Foundation, National Cancer Institute, National Research Service Award CA-09338,D ivisiono f Cancer Preventiona nd Control, and Surgical Research Inc. Presented at the Fifty-seventhA nnual Meeting of the Society of University Surgeons, Washington,D .C., Feb. 8-10, 1996. Reprint requests:W illiamJ . Schirmer, MD, The Ohio State University, N724 Doan Hall, 410 W. Tenth Ave., Columbus,O H 43210. Copyright 9 1996 by Mosby-Year Book, Inc. 0039-6060/96/$5.00 + 11/6/73520 relatively nontoxic agents in adjuvant therapy of pancreatic cancer.
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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U2 - 10.1016/S0039-6060(96)80293-5
DO - 10.1016/S0039-6060(96)80293-5
M3 - Article
C2 - 8751588
AN - SCOPUS:0029822870
SN - 0039-6060
VL - 120
SP - 234
EP - 241
JO - Surgery
JF - Surgery
IS - 2
ER -
