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Paper| Volume 30, ISSUE 11, P1682-1687, 1994

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Somatostatin receptor expression in lung cancer

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      Abstract

      Experimental evidence suggests that somatostatin analogues may have a role to play in the management of lung tumours. We evaluated membrane preparations of nine small cell lung cancer (SCLC) cell lines and of tumour samples from 3 patients with non-small cell lung cancer (NSCLC), 1 patient with an atypical carcinoid and another with a bronchial carcinoid for the presence of specific binding sites for RC-160, a potent growth inhibitory octapeptide analogue of somatostatin. Specific binding was noted on six of nine SCLC lines. Radio-receptor assay on the cell line NCI H 69 showed evidence of two specific binding sites for RC-160, one with high affinity and the other with low affinity. Binding sites were also found on all five tumour samples. Scatchard analysis indicated the presence of a single class of receptors with high affinity in each case. Histological assessment of the resected specimens before binding assay showed them to be comprised of tumour cells and necrotic tissue, stroma and/or inflammatory cells. Therefore, the specific binding of RC-160 may be to tissues other than the tumour cells. In 3 patients, from whom the tumour samples were obtained, radiolabelled somatostatin analogue scintigraphy using [111In] pentetreotide was performed prior to surgery. In all cases, the radiolabel localised the disease. This study demonstrates the presence of specific binding sites for RC-160 in SCLC. Furthermore, the detection of specific binding in vitro and in vivo in NSCLC and intrapulmonary carcinoids demonstrates that these tumours contain cells which express specific binding sites for somatostatin. These results suggest that RC-160 may have a role to play as a therapeutic agent in lung cancer.

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      References

        • O'Byrne K.J.
        • Carney D.N.
        Somatostatin and the lung.
        Lung Cancer. 1993; 10: 151-172
        • Taylor J.E.
        • Coy D.H.
        • Moreau J-P.
        High affinity binding of [125ITyr11] somatostatin-14 to human small-cell carcinoma (NCI-H69).
        Life Sci. 1988; 43: 421-427
        • Reubi J.C.
        • Waser B.
        • Sheppard M.
        • Macauley V.
        Somatostatin receptors are present in small-cell but not in non-small-cell primary lung carcinomas: relationship to EGF-receptors.
        Int J Cancer. 1990; 45: 269-274
        • Macaulay V.M.
        • Smith I.E.
        • Everard M.J.
        • Teale J.D.
        • Reubi J-C.
        • Millar J.L.
        Experimental and clinical studies with somatostatin analogue octreotide in small cell lung cancer.
        Br J Cancer. 1991; 64: 451-456
        • Sagman U.
        • Mullen B.
        • Kovacs K.
        • Kerbel R.
        • Ginsberg R.
        • Reubi J-C.
        Identification of somatostatin receptors in human small cell lung carcinoma.
        Cancer. 1990; 66: 2129-2133
        • Bogden A.E.
        • Taylor J.E.
        • Moreau J-P.
        • Coy D.H.I.
        • LePage D.J.
        Response of human lung xenografts to treatment with a somatostatin analogue (somatuline).
        Cancer Res. 1990; 50: 4360-4365
        • Kwekkeboom D.J.
        • Krenning E.P.
        • Bakker W.H.
        • et al.
        Radioiodinated somatostatin analog scintigraphy in small-cell lung cancer.
        J Nucl Med. 1991; 32: 1845-1848
        • O'Byrne K.J.
        • Ennis J.T.
        • Freyne P.J.
        • Clancy L.J.
        • Prichard J.S.
        • Carney D.N.
        Scintigraphic imaging of small cell lung cancer patients with 111In-pentetreotide, a radiolabelled octapeptide analogue of somatostatin.
        Br J Cancer. 1994; 69: 762-766
        • Schally A.V.
        • Cai R-Z.
        • Aleman T.
        • et al.
        Endocrine, gastrointestinal and antitumour activity of somatostatin analogues.
        in: Moody T.W. Neural and Endocrine Peptides and Receptors. 1986: 73-88
        • Schally A.V.
        Oncological applications of somatostatin analogues. Perspectives in cancer research.
        Cancer Res. 1988; 48: 6977-6985
        • Brower S.T.
        • Schally A.V.
        • Redding T.W.
        • Hollander V.P.
        Differential effects of LHRH and somatostatin analogs on human breast cancer.
        J Surg Res. 1992; 52: 6-14
        • Szepeshazi K.
        • Schally A.V.
        • Cai R-Z.
        • Radulovic S.
        • Milovanovic S.
        • Szoke B.
        Inhibitory effect of bombesin/gastrin-releasing peptide antagonist RC-3095 and high dose somatostatin analogue RC-160 on nitrosamine-induced pancreatic cancers in hamsters.
        Cancer Res. 1991; 51: 5980-5986
        • Qin Y.
        • Schally A.V.
        • Willems G.
        Somatostatin analogue RC-160 inhibits the growth of transplanted colon cancer in rats.
        Int J Cancer. 1991; 47: 765-770
        • Schally A.V.
        • Redding T.W.
        Somatostatin analogs as adjuncts to agonists of leuteinizing hormone releasing-hormone in the treatment of experimental prostate cancer.
        in: Proc Natl Acad Sci USA. 84. 1987: 7275-7279
        • Greenwood F.C.
        • Hunter W.H.
        • Glover J.S.
        The preparation of 131I labelled growth hormone of high specific radioactivity.
        Biochemistry. 1963; 89: 114-123
        • Mason-Garcia M.
        • Vaccarella M.
        • Horvath J.
        • et al.
        Radioimmunoassay for octapeptide analogs of somatostatin: measurement of serum levels after administration of long-acting microcapsule formulations.
        in: Proc Natl Acad Sci USA. 85. 1988: 5688-5692
        • Bradford M.M.
        A rapid and sensitive method for the quantitation of microgram quantities of protein utilising the principle of protein-dye binding.
        Anal Biochem. 1976; 72: 248-254
        • Srkalovic G.
        • Cai R-Z.
        • Schally A.V.
        Evaluation of receptors for somatostatin in various tumours using different analogs.
        J Clin Endo Metab. 1990; 70: 661-669
        • Munson P.J.
        • Rodbard D.
        A versatile computerised approach for characterization of ligand-binding systems.
        Anal Biochem. 1980; 107: 220-239
        • McPherson G.A.
        Analysis of radioligand binding experiments: a collection of computer programs for the IBM PC.
        J Pharmacol Meth. 1985; 14: 213-228
        • Scatchard G.
        The attraction of proteins for small molecules and ions.
        Ann NY Acad Sci USA. 1949; 51: 660-675
        • Carney D.N.
        The biology of lung cancer.
        Curr Opin Oncol. 1992; 4: 292-298
        • Hansen H.H.
        Management of small-cell lung cancer of the lung.
        Lancet. 1992; 339: 846-849
        • Souquet P.J.
        • Chauvin F.
        • Boissel J.P.
        • et al.
        Polychemotherapy in advanced non-small-cell lung cancer: a meta-analysis.
        Lancet. 1993; 342: 19-21
        • Ihde D.C.
        Drug therapy: chemotherapy of lung cancer.
        N Engl J Med. 1992; 327: 1434-1441
        • Reubi J-C.
        • Kvols L.
        • Krenning E.
        • Lamberts S.W.J.
        Distribution of somatostatin receptors in normal and tumor tissue.
        Metabolism. 1990; 39: 78-81
        • Sreedharan S.P.
        • Kodama K.T.
        • Peterson K.E.
        • Goetzl E.J.
        Distinct subsets of somatostatin receptors on cultured human lymphocytes.
        J Biol Chem. 1989; 264: 949-952
        • Krenning E.P.
        • Kwekkeboom J.D.
        • Bakker W.H.
        Somatostatin receptor scintigraphy with [111In-DTPA-D-Phe1]- and [123ITyr3]-octreotide: the Rotterdam experience with more than 1000 patients.
        Eur J Nucl Med. 1993; 20: 716-731
        • Yamada Y.
        • Post S.R.
        • Wang K.
        • Tager H.S.
        • Bell G.I.
        • Seino S.
        Cloning and functional characteristics of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal tract and kidney.
        in: Proc Natl Acad Sci USA. 89. 1992: 251-255
        • Yasuda K.
        • Rens-Domiano S.
        • Breder C.D.
        • et al.
        Cloning of a novel somatostatin receptor, SSTR3, coupled to adenylylcyclase.
        J Biol Chem. 1992; 267: 20422-20428
        • Bruno J.F.
        • Xu U.
        • Song J.
        • Berelowitz M.
        Molecular cloning and functional expression of a brain-specific somatostatin receptor.
        in: Proc Natl Acad Sci USA. 89. 1992: 11151-11155
        • Raynor K.
        • O'Carroll A.M.
        • Kong H.
        • et al.
        Characterisation of cloned somatostatin receptors SSTR4 and SSTR5.
        Mol Pharmacol. 1993; 44: 385-392
        • Rohrer L.
        • Raulf F.
        • Buns C.
        • Buettner R.
        • Hofstaedter F.
        • Schule R.
        Cloning and characterisation of a fourth human somatostatin receptor.
        in: Proc Natl Acad Sci USA. 90. 1993: 4192-4200
        • Buscail L.
        • Delesque N.
        • Esteve J.-P.
        • et al.
        Stimulation of tyrosine phosphatase and inhibition of cell proliferation by somatostatin analogues: mediation by human somatostatin receptor subsets SSTR1 and SSTR2.
        in: Proc Natl Acad Sci USA. 91. 1994: 2315-2319
        • Ghirlanda G.
        • Uccioli L.
        • Perri F.
        • et al.
        Epidermal growth factor, somatostatin, and psoriasis.
        Lancet. 1983; 1A: 65