This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Buscail, L. Articles by Susini, C. Search for Related Content PubMed PubMed Citation Articles by Buscail, L. Articles by Susini, C.

Loss of sst2 Somatostatin Receptor Gene Expression in Human Pancreatic and Colorectal Cancer¹

INSERM U151, Institut Louis Bugnard, I avenue J. Poulhès, CHU Rangueil, 31054 Toulouse, Cédex, France [L. B., N. S-L., N. V., C. S.]; INSERM U55 and Service de Chirurgie Digestive, Hôpital Saint Antoine, 75012 Paris, France [E. C., J-C. V., C. G.]; Laboratori d'Investigacio Gastrointestinal, Institut de Recerca, Hospital de la Santa Creu I Sant Pau, 08025 Barcelona, Spain [G. C., F. L.]; and Research Unit Molecular Oncology, University Hospital, 24105 Kiel, Germany [H. K.]

Five somatostatin receptor subtypes (sst1 to sst5) have been cloned. We demonstrated previously that sst2 and sst5 mediate the antiproliferative effect of the somatostatin analogues octreotide and vapreotide. Using reverse transcription-PCR, we investigated gene expression of the five receptors in 47 human normal and cancerous tissues or cell lines from pancreatic and colorectal origin. mRNAs of somatostatin receptor subtypes were detected in 98% of samples, with more than two mRNA subtypes being expressed in 55% of cases. sst1, sst4, and sst5 were heterogeneously expressed in both normal and cancerous tissues; sst3 was rarely or not expressed. sst2 was present in normal pancreatic tissues but was absent in exocrine pancreatic carcinomas and their metastases. sst2 mRNAs were detected in normal colon, sporadic polyadenomas, and 50% of Dukes' stage B and 20% of Dukes' stage C carcinomas but were undetectable in Dukes' stage D carcinomas, hepatic metastases, and adenomas from familial adenomatous polyposis. The loss of sst2 expression could represent a growth advantage in these tumors and provide an explanation for the lack of therapeutic effect of somatostatin analogues in such adenocarcinomas. A subtyping of somatostatin receptors should be carried out before considering a somatostatin analogue treatment in patients with colorectal or pancreatic cancer.

¹ Supported in part by Grant 6755 from the Association pour la Recherche contre le Cancer; Grant 9200045 from the Conseil Régional Midi Pyrénées; a grant from the Institut de Recherche des Maladies de l'Appareil Digestif; Grant SAL91-0873 from the Plan Nacional I + D, Spain; and Grant FIS 94-0001-1 from The Fondo de Investigaciones Sanitarias, Spain.

² To whom requests for reprints should be addressed. Phone: (33) 61 32 24 01; Fax: (33) 62 26 40 12.

Received 10/20/95. Accepted 2/14/96.

This article has been cited by other articles:

				H. Laklai, S. Laval, L. Dumartin, P. Rochaix, M. Hagedorn, A. Bikfalvi, S. Le Guellec, M.-B. Delisle, A. V. Schally, C. Susini, et al. Thrombospondin-1 is a critical effector of oncosuppressive activity of sst2 somatostatin receptor on pancreatic cancer PNAS, October 20, 2009; 106(42): 17769 - 17774. [Abstract] [Full Text] [PDF]

				Z. Zhang, Y. Huang, K. Newman, J. Gu, X. Zhang, H. Wu, M. Zhao, Z. Xianyu, and X. Liu Reexpression of Human Somatostatin Receptor Gene 2 Gene Mediated by Oncolytic Adenovirus Increases Antitumor Activity of Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand against Pancreatic Cancer Clin. Cancer Res., August 15, 2009; 15(16): 5154 - 5160. [Abstract] [Full Text] [PDF]

				J. Acunzo, S. Thirion, C. Roche, A. Saveanu, G. Gunz, A. L. Germanetti, B. Couderc, R. Cohen, D. Figarella-Branger, H. Dufour, et al. Somatostatin Receptor sst2 Decreases Cell Viability and Hormonal Hypersecretion and Reverses Octreotide Resistance of Human Pituitary Adenomas Cancer Res., December 15, 2008; 68(24): 10163 - 10170. [Abstract] [Full Text] [PDF]

				F. P. Leu, M. Nandi, and C. Niu The Effect of Transforming Growth Factor {beta} on Human Neuroendocrine Tumor BON Cell Proliferation and Differentiation Is Mediated through Somatostatin Signaling Mol. Cancer Res., June 1, 2008; 6(6): 1029 - 1042. [Abstract] [Full Text] [PDF]

				J. Torrisani, N. Hanoun, H. Laurell, F. Lopez, J.-J. Maoret, A. Souque, C. Susini, P. Cordelier, and L. Buscail Identification of an Upstream Promoter of the Human Somatostatin Receptor, hSSTR2, Which Is Controlled by Epigenetic Modifications Endocrinology, June 1, 2008; 149(6): 3137 - 3147. [Abstract] [Full Text] [PDF]

				A. Asnacios, F. Courbon, P. Rochaix, E. Bauvin, V. Cances-Lauwers, C. Susini, S. Schulz, A. Boneu, R. Guimbaud, and L. Buscail Indium-111-Pentetreotide Scintigraphy and Somatostatin Receptor Subtype 2 Expression: New Prognostic Factors for Malignant Well-Differentiated Endocrine Tumors J. Clin. Oncol., February 20, 2008; 26(6): 963 - 970. [Abstract] [Full Text] [PDF]

				C Susini and L Buscail Rationale for the use of somatostatin analogs as antitumor agents Ann. Onc., December 1, 2006; 17(12): 1733 - 1742. [Abstract] [Full Text] [PDF]

				S. V. de Sa, M. L. Correa-Giannella, M. C. Machado, J. J. S de Souza, M. A. A. Pereira, R. A. Patzina, S. A. C. Siqueira, M. C. C. Machado, and D. Giannella-Neto Somatostatin receptor subtype 5 (SSTR5) mRNA expression is related to histopathological features of cell proliferation in insulinomas. Endocr. Relat. Cancer, March 1, 2006; 13(1): 69 - 78. [Abstract] [Full Text] [PDF]

				H. Lahlou, M. Fanjul, L. Pradayrol, C. Susini, and S. Pyronnet Restoration of Functional Gap Junctions through Internal Ribosome Entry Site-Dependent Synthesis of Endogenous Connexins in Density-Inhibited Cancer Cells Mol. Cell. Biol., May 15, 2005; 25(10): 4034 - 4045. [Abstract] [Full Text] [PDF]

				S.-H. Tseng, Y. Chen, C.-J. Chang, K.-F. Tai, S.-M. Lin, and L.-H. Hwang Induction of T-Cell Apoptosis in Rats by Genetically Engineered Glioma Cells Expressing Granulocyte-Macrophage Colony-Stimulating Factor and B7.1 Clin. Cancer Res., February 15, 2005; 11(4): 1639 - 1649. [Abstract] [Full Text] [PDF]

				M. Ginj, J. Chen, M. A. Walter, V. Eltschinger, J. C. Reubi, and H. R. Maecke Preclinical Evaluation of New and Highly Potent Analogues of Octreotide for Predictive Imaging and Targeted Radiotherapy Clin. Cancer Res., February 1, 2005; 11(3): 1136 - 1145. [Abstract] [Full Text] [PDF]

				D. J. Buchsbaum, T. R. Chaudhuri, and K. R. Zinn Radiotargeted Gene Therapy J. Nucl. Med., January 1, 2005; 46(1_suppl): 179S - 186S. [Abstract] [Full Text] [PDF]

				M. Kumar, Z.-R. Liu, L. Thapa, and R.-Y. Qin Anti-angiogenic effects of somatostatin receptor subtype 2 on human pancreatic cancer xenografts Carcinogenesis, November 1, 2004; 25(11): 2075 - 2081. [Abstract] [Full Text] [PDF]

				L. Barzon, M. Boscaro, and G. Palu Endocrine Aspects of Cancer Gene Therapy Endocr. Rev., February 1, 2004; 25(1): 1 - 44. [Abstract] [Full Text] [PDF]

				J. Bertherat, F. Tenenbaum, K. Perlemoine, C. Videau, J. L. Alberini, B. Richard, B. Dousset, X. Bertagna, and J. Epelbaum Somatostatin Receptors 2 and 5 Are the Major Somatostatin Receptors in Insulinomas: An in Vivo and in Vitro Study J. Clin. Endocrinol. Metab., November 1, 2003; 88(11): 5353 - 5360. [Abstract] [Full Text] [PDF]

				J. C. Reubi Peptide Receptors as Molecular Targets for Cancer Diagnosis and Therapy Endocr. Rev., August 1, 2003; 24(4): 389 - 427. [Abstract] [Full Text] [PDF]

				S. Faiss, U.-F. Pape, M. Bohmig, Y. Dorffel, U. Mansmann, W. Golder, E. O. Riecken, and B. Wiedenmann Prospective, Randomized, Multicenter Trial on the Antiproliferative Effect of Lanreotide, Interferon Alfa, and Their Combination for Therapy of Metastatic Neuroendocrine Gastroenteropancreatic Tumors--The International Lanreotide and Interferon Alfa Study Group J. Clin. Oncol., July 15, 2003; 21(14): 2689 - 2696. [Abstract] [Full Text] [PDF]

				J. C. Reubi, B. Waser, W. Vale, and J. Rivier Expression of CRF1 and CRF2 Receptors in Human Cancers J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3312 - 3320. [Abstract] [Full Text] [PDF]

				J. Guillermet, N. Saint-Laurent, P. Rochaix, O. Cuvillier, T. Levade, A. V. Schally, L. Pradayrol, L. Buscail, C. Susini, and C. Bousquet Somatostatin receptor subtype 2 sensitizes human pancreatic cancer cells to death ligand-induced apoptosis PNAS, January 7, 2003; 100(1): 155 - 160. [Abstract] [Full Text] [PDF]

				G Z Racz, A Kittel, D Riccardi, R M Case, A C Elliott, and G Varga Extracellular calcium sensing receptor in human pancreatic cells Gut, November 1, 2002; 51(5): 705 - 711. [Abstract] [Full Text] [PDF]

				F. Vernejoul, P. Faure, N. Benali, D. Calise, G. Tiraby, L. Pradayrol, C. Susini, and L. Buscail Antitumor Effect of in Vivo Somatostatin Receptor Subtype 2 Gene Transfer in Primary and Metastatic Pancreatic Cancer Models Cancer Res., November 1, 2002; 62(21): 6124 - 6131. [Abstract] [Full Text] [PDF]

				K. Szepeshazi, A. V. Schally, G. Halmos, P. Armatis, F. Hebert, B. Sun, A. Feil, H. Kiaris, and A. Nagy Targeted Cytotoxic Somatostatin Analogue AN-238 Inhibits Somatostatin Receptor-positive Experimental Colon Cancers Independently of Their p53 Status Cancer Res., February 1, 2002; 62(3): 781 - 788. [Abstract] [Full Text] [PDF]

				C. C. Raggi, A. Calabro, D. Renzi, V. Briganti, F. Cianchi, L. Messerini, R. Valanzano, M. C. Smith, C. Cortesini, F. Tonelli, et al. Quantitative Evaluation of Somatostatin Receptor Subtype 2 Expression in Sporadic Colorectal Tumor and in the Corresponding Normal Mucosa Clin. Cancer Res., February 1, 2002; 8(2): 419 - 427. [Abstract] [Full Text] [PDF]

				C Gouillat and J-F Gigot Pancreatic surgical complications--the case for prophylaxis Gut, December 1, 2001; 49(90004): iv29 - 35. [Abstract] [Full Text] [PDF]

				K. Szepeshazi, A. V. Schally, G. Halmos, B. Sun, F. Hebert, B. Csernus, and A. Nagy Targeting of Cytotoxic Somatostatin Analog AN-238 to Somatostatin Receptor Subtypes 5 and/or 3 in Experimental Pancreatic Cancers Clin. Cancer Res., September 1, 2001; 7(9): 2854 - 2861. [Abstract] [Full Text] [PDF]

				Y. Chowers, L. Cahalon, M. Lahav, H. Schor, R. Tal, S. Bar-Meir, and M. Levite Somatostatin Through Its Specific Receptor Inhibits Spontaneous and TNF-{alpha}- and Bacteria-Induced IL-8 and IL-1{beta} Secretion from Intestinal Epithelial Cells J. Immunol., September 15, 2000; 165(6): 2955 - 2961. [Abstract] [Full Text] [PDF]

				A. Plonowski, A. V. Schally, A. Nagy, H. Kiaris, F. Hebert, and G. Halmos Inhibition of Metastatic Renal Cell Carcinomas Expressing Somatostatin Receptors by a Targeted Cytotoxic Analogue of Somatostatin AN-238 Cancer Res., June 1, 2000; 60(11): 2996 - 3001. [Abstract] [Full Text] [PDF]

				N. Baou, M. Bouras, J.-P. Droz, M. Benahmed, and S. Krantic Evidence for a selective loss of somatostatin receptor subtype expression in male germ cell tumors of seminoma type Carcinogenesis, April 1, 2000; 21(4): 805 - 810. [Abstract] [Full Text] [PDF]

				T. Stroh, A. C. Jackson, P. Sarret, C. Dal Farra, J.-P. Vincent, H.-J. Kreienkamp, J. Mazella, and A. Beaudet Intracellular Dynamics of sst5 Receptors in Transfected COS-7 Cells: Maintenance of Cell Surface Receptors during Ligand-Induced Endocytosis Endocrinology, January 1, 2000; 141(1): 354 - 365. [Abstract] [Full Text] [PDF]

				N. Kimura, M. Pilichowska, F. Date, I. Kimura, and M. Schindler Immunohistochemical Expression of Somatostatin Type 2A Receptor in Neuroendocrine Tumors Clin. Cancer Res., November 1, 1999; 5(11): 3483 - 3487. [Abstract] [Full Text] [PDF]

				N. Douziech, E. Calvo, Z. Coulombe, G. Muradia, J. Bastien, R. A. Aubin, A. Lajas, and J. Morisset Inhibitory and Stimulatory Effects of Somatostatin on Two Human Pancreatic Cancer Cell Lines: A Primary Role for Tyrosine Phosphatase SHP-1 Endocrinology, February 1, 1999; 140(2): 765 - 777. [Abstract] [Full Text]

				J. C. Reubi, A. Kappeler, B. Waser, J. Laissue, R. W. Hipkin, and A. Schonbrunn Immunohistochemical Localization of Somatostatin Receptors sst2A in Human Tumors Am. J. Pathol., July 1, 1998; 153(1): 233 - 245. [Abstract] [Full Text] [PDF]

				J C Reubi, B Waser, H Friess, M Buchler, and J Laissue Neurotensin receptors: a new marker for human ductal pancreatic adenocarcinoma Gut, April 1, 1998; 42(4): 546 - 550. [Abstract] [Full Text] [PDF]

				P. Caron, L. Buscail, A. Beckers, J.-P. Esteve, A. Igout, G. Hennen, and C. Susini Expression of Somatostatin Receptor SST4 in Human Placenta and Absence of Octreotide Effect on Human Placental Growth Hormone Concentration during Pregnancy J. Clin. Endocrinol. Metab., November 1, 1997; 82(11): 3771 - 3776. [Abstract] [Full Text] [PDF]

				P. Cordelier, J.-P. Esteve, C. Bousquet, N. Delesque, A.-M. O'Carroll, A. V. Schally, N. Vaysse, C. Susini, and L. Buscail Characterization of the antiproliferative signal mediated by the somatostatin receptor subtype sst5 PNAS, August 19, 1997; 94(17): 9343 - 9348. [Abstract] [Full Text] [PDF]

				A. A. Sinisi, A. Bellastella, D. Prezioso, M. R. Nicchio, T. Lotti, M. Salvatore, and D. Pasquali Different Expression Patterns of Somatostatin Receptor Subtypes in Cultured Epithelial Cells from Human Normal Prostate and Prostate Cancer J. Clin. Endocrinol. Metab., August 1, 1997; 82(8): 2566 - 2569. [Abstract] [Full Text] [PDF]

				E. Puente, N. Saint-Laurent, J. Torrisani, C. Furet, A. V. Schally, N. Vaysse, L. Buscail, and C. Susini Transcriptional Activation of Mouse sst2 Somatostatin Receptor Promoter by Transforming Growth Factor-beta . INVOLVEMENT OF Smad4 J. Biol. Chem., April 13, 2001; 276(16): 13461 - 13468. [Abstract] [Full Text] [PDF]

				N. Benali, P. Cordelier, D. Calise, P. Pages, P. Rochaix, A. Nagy, J.-P. Esteve, P. M. Pour, A. V. Schally, N. Vaysse, et al. Inhibition of growth and metastatic progression of pancreatic carcinoma in hamster after somatostatin receptor subtype 2 (sst2) gene expression and administration of cytotoxic somatostatin analog AN-238 PNAS, August 1, 2000; 97(16): 9180 - 9185. [Abstract] [Full Text] [PDF]

				J. C. Reubi, J.-C. Schaer, S. Wenger, C. Hoeger, J. Erchegyi, B. Waser, and J. Rivier SST3-selective potent peptidic somatostatin receptor antagonists PNAS, December 5, 2000; 97(25): 13973 - 13978. [Abstract] [Full Text] [PDF]