[en] Malignant growth of small-cell lung carcinoma is promoted by various neuroendocrine autocrine/paracrine loops. Therefore, to interfere with this mitogenic process, it is crucial to elucidate the mechanisms involved. It is known that the oxytocin (OT) and vasopressin (VP) genes, normally transcriptionally restricted in their expression, are activated in small-cell lung cancer (SCLC), concomitantly with expression of their receptors (OTR, V1aR, V1bR/V3R and V2R). The aim of the present study was to characterize, in concentrations close to physiological and pharmacological conditions, intracellular signalling events triggered by OT and VP binding to their specific receptors in SCLC cells and to identify factors mediating OT- and VP-induced mitogenic effects on SCLC. Known agonists for OTR ([Thr(4),GlY(7)]OT) and V1aR (F180), in addition to OT and VP, were able to elicit increases in cytosolic Ca2+ levels and this effect could be blocked using an OTR antagonist (OVTA) or a V1aR antagonist (SR49059) respectively. There was no activation of the cAMP pathway detected after VP, dDAVP (a V2R agonist), or OT treatment. Stimulation of SCLC cells with OT and VP led to an increase of extracellular signal-regulated kinase (ERK) 1/2 phosphorylation, maximal at 5 min, and the subsequent phosphorylation of its downstream target p90 ribosomal S6 kinase (p90(RSK)). Pre-incubation with OVTA and SR49059, and with inhibitors of phospholipase C (PLC), protein kinase C (PKC), mitogen-activated protein kinase/ERK kinase (MEK) 1/2 and a Ca2+ chelator significantly reduced OT- and VP-induced ERK1/2 phosphorylations. OVTA, SR49059 as well as MEK1/2 and PKC inhibitors also downregulated OT- and VP-induced p90RSK phosphorylation. In [H-3]thymidine-uptake 2, experiments, we subsequently observed that PLC, Ca2+, PKC and ERK1/2 are absolutely required for the OT- and VP-stimulated SCLC cellular growth process. In conclusion, the results presented here indicate that OT- and VP-induced mitogenic effects on SCLC are respectively mediated by OTR and V1aR signalling and that this mitogenic signalling passes through the phosphorylation of ERK1/2 and p90(RSK) in a PLC-, Ca2+-, PKC- and MEK1/2-dependent pathway.
Disciplines :
Oncology Endocrinology, metabolism & nutrition
Author, co-author :
Pequeux, Christel ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Keegan, B. P.
Hagelstein, M. T.
Geenen, Vincent ; Université de Liège - ULiège > Centre d'immunologie
Legros, Jean-Jacques ; Université de Liège - ULiège > Département des sciences cliniques > Département des sciences cliniques
North, W. G.
Language :
English
Title :
Oxytocin- and vasopressin-induced growth of human small-cell lung cancer is mediated by the mitogen-activated protein kinase pathway
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Bibliography
Andres M, Trueba M & Guillon G 2002 Pharmacological characterization of F-180: a selective human V(1a) vasopressin receptor agonist of high affinity. British Journal of Pharmacology 135 1828-1836.
Aurell C, Bengtsson B, Ekholm K, Kasprzykowska R, Nilsson A, Persson A, Trojnar J, Abbe M & Melin P 1990 Development of vasopressor specific vasotocin analogues with prolonged effects. In Peptides, pp 671-673. Eds E Giralt & D Andreu. Leiden, The Netherlands: ESCOM Science Publishers.
Barberis C, Mouillac B & Durroux T 1998 Structural bases of vasopressin/oxytocin receptor function. Journal of Endocrinology 156 223-229.
Barberis C, Morin D, Durroux T, Mouillac B, Guillon G, Seyer R, Hibert M, Tribollet E & Manning M 1999 Molecular pharmacology of AVP and OT receptors and therapeutic potential. Drug News Perspective 12 279-292.
Birnbaumer M, Seibold A, Gilbert S, Ishido M, Barberis C, Antaramian A, Brabet P & Rosenthal W 1992 Molecular cloning of the receptor for human antidiuretic hormone. Nature 357 333-335.
Bunn PA Jr, Chan D, Stewart J, Gera L, Tolley R, Jewett P, Tagawa M, Alford C, Mochzuki T & Yanaihara N 1994 Effects of neuropeptide analogues on calcium flux and proliferation in lung cancer cell lines. Cancer Research 54 3602-3610.
Bussolati G & Cassoni P 2001 Editorial: the oxytocin/oxytocin receptor system-expect the unexpected. Endocrinology 142 1377-1379.
Cassoni P, Sapino A, Fortunati N, Munaron L, Chini B & Bussolati G 1997 Oxytocin inhibits the proliferation of MDA-MB231 human breast-cancer cells via cyclic adenosine monophosphate and protein kinase A. International Journal of Cancer 72 340-344.
Cassoni P, Sapino A, Stella A & Bussolati G 1998 Antiproliferative effect of oxytocin through specific oxytocin receptors in human neuroblastoma and astrocytoma cell lines. Advances in Experimental Medicine and Biology 449 245-246.
Cassoni P, Marrocco T, Deaglio S, Sapino A & Bussolati G 2001 Biological relevance of oxytocin and oxytocin receptors in cancer cells and primary tumors. Annals of Oncology 12 S37-S39.
Cassoni P, Sapino A, Deaglio S, Bussolati B, Volante M, Munaron L, Albini A, Torrisi A & Bussolati G 2002 Oxytocin is a growth factor for Kaposi's sarcoma cells: evidence of endocrine-immunological cross-talk. Cancer Research 62 2406-2413.
Chiu T, Wu SS, Santiskulvong C, Tangkijvanich P, Yee HF Jr & Rozengurt E 2002 Vasopressin-mediated mitogenic signaling in intestinal epithelial cells. American Journal of Physiology, Cell Physiology 282 C434-C450.
de Keyzer Y, Auzan C, Lenne F, Beldjord C, Thibonnier M, Bertagna X & Clauser E 1994 Cloning and characterization of the human V3 pituitary vasopressin receptor. FEBS Letters 356 215-220.
Devost D & Zingg HH 2004 Homo- and hetero-dimeric complex formations of the human oxytocin receptor. Journal of Neuroendocrinology 16 372-377.
Friedmann AS, Malott KA, Memoli VA, Pai SI, Yu XM & North WG 1994 Products of vasopressin gene expression in small-cell carcinoma of the lung. British Journal of Cancer 69 260-263.
Frodin M & Gammeltoft S 1999 Role and regulation of 90 kDa ribosomal S6 kinase (RSK) in signal transduction. Molecular and Cellular Endocrinology 151 65-77.
Guzzi F, Zanchetta D, Cassoni P, Guzzi V, Francolini M, Parenti M & Chini B 2002 Localization of the human oxytocin receptor in caveolin-1 enriched domains turns the receptor-mediated inhibition of cell growth into a proliferative response. Oncogens 21 1658-1667.
Hanahan D & Weinberg RA 2000 The hallmarks of cancer. Cell 100 57-70.
Heasley LE 2001 Autocrine and paracrine signaling through neuropeptide receptors in human cancer. Oncogene 20 1563-1569.
Hong M & Moody TW 1991 Vasopressin elevates cytosolic calcium in small cell lung cancer cells. Peptides 12 1315-1319.
Jard S 1998 Vasopressin receptors. A historical survey. In Advances in Experimental Medicine and Biology, pp 1-13. Eds HH Zing, CW Bourque & DG Bichet. New York: Plenum Press.
Johnson GL & Lapadat R 2002 Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298 1911-1912.
Kimura T, Tanizawa O, Mori K, Brownstein MJ & Okayama H 1992 Structure and expression of a human oxytocin receptor. Nature 356 526-529 [published erratum appears in Nature 357 176].
Kimura T, Tanizawa O, Mori K, Brownstein MJ & Okayama H 1992 Structure and expression of a human oxytocin receptor. Nature 356 526-529 [published erratum appears in Nature 357 176].
Lowbridge J, Manning M, Haldar J & Sawyer WH 1977 Synthesis and some pharmacological properties of [4-threonine, 7-glycine]oxytocin, [1-(L-2-hydroxy-3-mercaptopropanoic acid), 4-threonine, 7-glycine]oxytocin (hydroxy[Thr4, Gly7]oxytocin), and [7-Glycine]oxytocin, peptides with high oxytocic-antidiuretic selectivity. Journal of Medicinal Chemistry 20 120-123.
Mackay HJ & Twelves CJ 2003 Protein kinase C: a target for anticancer drugs? Endocrine-Related Cancer 10 389-396.
Manning M, Kruszynski M, Bankowski K, Olma A, Lammek B, Cheng LL, Klis WA, Seto J, Haldar J & Sawyer WH 1989 Solid-phase synthesis of 16 potent (selective and nonselective) in vivo antagonists of oxytocin. Journal of Medicinal Chemistry 32 382-391.
North WG 2000 Gene regulation of vasopressin and vasopressin receptors in cancer. Experimental Physiology 85 27S-40S.
North WG, Friedmann AS & Yu X 1993 Tumor biosynthesis of vasopressin and oxytocin. Annals of the New York Academy of Science 689 107-121.
North WG, Fay MJ, Longo K & Du J 1997 Functional vasopressin V1 type receptors are present in variant as well as classical forms of small-cell carcinoma. Peptides 18 985-993.
North WG, Fay MJ & Du J 1998a All three vasopressin receptor sub-types are expressed by small-cell carcinoma. Advances in Experimental Medicine and Biology 449 335-338.
North WG, Fay MJ, Longo KA & Du J 1998b Expression of all known vasopressin receptor subtypes by small cell tumors implies a multifaceted role for this neuropeptide. Cancer Research 58 1866-1871.
Ohmichi M, Koike K, Nohara A, Kanda Y, Sakamoto Y, Xian Zhang Z, Hirota K & Miyake A 1995 Oxytocin stimulates mitogen-activated protein kinase activity in cultured human puerperal uterine myometrial cells. Endocrinology 136 2082-2087.
Péqueux C, Breton C, Hendrick J-C, Hagelstein M-T, Martens H, Winkler R, Geenen V & Legros J-J 2002 Oxytocin synthesis and oxytocin receptor expression by cell lines of human small cell carcinoma of the lung stimulate tumor growth through an autocrine/paracrine signaling. Cancer Research 62 4623-4629.
Rimoldi V, Reversi A, Taverna E, Rosa P, Francolini M, Cassoni P, Parenti M & Chini B 2003 Oxytocin receptor elicits different EGFR/MAPK activation patterns depending on its localization in caveolin-1 enriched domains. Oncogene 22 6054-6060.
Rozengurt E 2002 Neuropeptides as growth factors for normal and cancerous cells. Trends in Endocrinology and Metabolism 13 128-134.
Sauer H, Klimm B, Hescheler J & Wartenberg M 2001 Activation of p90RSK and growth stimulation of multicellular tumor spheroids are dependent on reactive oxygen species generated after purinergic receptor stimulation by ATP. FASEB Journal 152539-2541.
Serradeil-Le Gal C, Wagnon J, Garcia C, Lacour C, Guiraudou P, Christophe B, Villanova G, Nisato D, Maffrand JP, Le Fur G, et al. 1993 Biochemical and pharmacological properties of SR 49059, a new, potent, nonpeptide antagonist of rat and human vasopressin Via receptors. Journal of Clinical Investigation 92 224-231.
Sethi T & Rozengurt E 1991 Multiple neuropeptides stimulate clonal growth of small cell lung cancer: effects of bradykinin, vasopressin, cholecystokinin, galanin, and neurotensin. Cancer Research 51 3621-3623.
Seufferlein T & Rozengurt E 1996 Galanin, neurotensin, and phorbol esters rapidly stimulate activation of mitogen-activated protein kinase in small cell lung cancer cells. Cancer Research 56 5758-5764.
Strakova Z, Copland JA, Lolait SJ & Soloff MS 1998 ERK2 mediates oxytocin-stimulated PGE2 synthesis. American Journal of Physiology, Endocrinology and Metabolism 274 E634-E641.
Sugimoto T, Saito M, Mochizuki S, Watanabe Y, Hashimoto S & Kawashimah 1994 Molecular cloning and functional expression of a cDNA encoding the human V1b vasopressin receptor. Journal of Biological Chemistry 269 27088-27092.
Terrillon S, Durroux T, Mouillac B, Breit A, Ayoub MA, Taulan M, Jockers R, Barberis C & Bouvier M 2003 Oxytocin and vasopressin Via and V2 receptors form constitutive homo- and heterodimers during biosynthesis. Molecular Endocrinology 17 677-691.
Thibonnier M, Auzan C, Madhiin Z, Wilkins P, Berti-Mattera L & Clauser E 1994 Molecular cloning, sequencing, and functional expression of a cDNA encoding the human Via vasopressin receptor. Journal of Biological Chemistry 269 3304-3310.
Thibonnier M, Conarty DM & Plesnicher CL 2000 Mediators of the mitogenic action of human V(1) vascular vasopressin receptors. American Journal of Physiology, Heart and Circulatory Physiology 279 H2529-H2539.
Willard FS & Crouch MF 2001 MEK, ERK, and p90RSK are present on mitotic tubulin in Swiss 3T3 cells: a role for the MAP kinase pathway in regulating mitotic exit. Cellular Signalling 13 653-664.
Woll PJ & Rozengurt E 1989a Neuropeptides as growth regulators. British Medicine Bulletin 45 492-505.
Woll PJ & Rozengurt E 1989b Multiple neuropeptides mobilise calcium in small cell lung cancer: effects of vasopressin, bradykinin, cholecystokinin, galanin and neurotensin. Biochemistry and Biophysics Research Communication 164 66-73.
Zaoral M, Kolc J & Sorm F 1967 Synthesis of 1-desamino-8-D-lysine vasopressin and 1-desamino-D-arginine vasopressin. Collection of Czech Chemistry Communication 32 1250-1257.
Zingg HH & Laporte SA 2003 The oxytocin receptor. Trends in Endocrinology and Metabolism 14 222-227.
Zochbauer-Muller S, Gazdar AF & Minna JD 2002 Molecular pathogenesis of lung cancer. Annual Review of Physiology 64 681-708.
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