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 Cattaneo, M. G. Articles by Sher, E. Search for Related Content PubMed PubMed Citation Articles by Cattaneo, M. G. Articles by Sher, E.

Nicotine Stimulates a Serotonergic Autocrine Loop in Human Small-Cell Lung Carcinoma¹

Consiglio Nazionale delle Ricerche Center of Cytopharmacology [A. C., F. C., E. S.] and Department of Medical Pharmacology, [M. G. C., L. M. V.] University of Milan, 20129 Milan, Italy

Small-cell lung carcinoma cells express different plasma membrane nicotinic acetylcholine receptor subtypes. We have now found that interacting with these receptors (-)-nicotine induces a dose-dependent and stereoselective release of [³H]serotonin which is dependent on external calcium and blocked by the specific ganglionic nicotinic antagonist mecamylamine. With the same potency (-)-nicotine stimulates tumor cell proliferation, an effect also blocked by mecamylamine. Serotonin itself stimulates cell proliferation in a dose-dependent manner, an effect blocked by the selective serotonergic receptor antagonists methiotepine and metergoline. These data suggest that nicotine might affect proliferation of small-cell lung carcinoma cells by inducing the release of hormones (such as serotonin) with autocrine capabilities and place both the nicotinic and the serotonergic receptors at key positions in the biological and, possibly, pharmacological approach to this human lung cancer.

¹ This work was supported by a grant from the National Research Council, Oriented Project "Clinical Application of Oncological Research" to L. M. V.

² M. G. C. is a recipient of a fellowship from Associazione Italiana per la Ricerca sul Cancro.

³ To whom requests for reprints should be addressed, at Consiglio Nazionale delle Ricerche Center of Cytopharmacology, Via Vanvitelli 32, 20129, Milan, Italy.

Received 6/28/93. Accepted 9/14/93.

This article has been cited by other articles:

				X. Sun, J. D. Ritzenthaler, X. Zhong, Y. Zheng, J. Roman, and S. Han Nicotine Stimulates PPAR{beta}/{delta} Expression in Human Lung Carcinoma Cells through Activation of PI3K/mTOR and Suppression of AP-2{alpha} Cancer Res., August 15, 2009; 69(16): 6445 - 6453. [Abstract] [Full Text] [PDF]

				L. Paleari, E. Negri, A. Catassi, M. Cilli, D. Servent, R. D'Angelillo, A. Cesario, P. Russo, and M. Fini Inhibition of Nonneuronal {alpha}7-Nicotinic Receptor for Lung Cancer Treatment Am. J. Respir. Crit. Care Med., June 15, 2009; 179(12): 1141 - 1150. [Abstract] [Full Text] [PDF]

				H. A. N. Al-Wadei, H. K. Plummer III, and H. M. Schuller Nicotine stimulates pancreatic cancer xenografts by systemic increase in stress neurotransmitters and suppression of the inhibitory neurotransmitter {gamma}-aminobutyric acid Carcinogenesis, March 1, 2009; 30(3): 506 - 511. [Abstract] [Full Text] [PDF]

				L. Paleari, P. Russo, L. Roz, A. Cesario, and U. Pastorino Smoking Out the Cholinergic Component in Lung Cancer Clin. Cancer Res., November 1, 2008; 14(21): 6742 - 6743. [Full Text] [PDF]

				A. Nocito, F. Dahm, W. Jochum, J. H. Jang, P. Georgiev, M. Bader, R. Graf, and P.-A. Clavien Serotonin Regulates Macrophage-Mediated Angiogenesis in a Mouse Model of Colon Cancer Allografts Cancer Res., July 1, 2008; 68(13): 5152 - 5158. [Abstract] [Full Text] [PDF]

				Y. Zheng, J. D. Ritzenthaler, J. Roman, and S. Han Nicotine Stimulates Human Lung Cancer Cell Growth by Inducing Fibronectin Expression Am. J. Respir. Cell Mol. Biol., December 1, 2007; 37(6): 681 - 690. [Abstract] [Full Text] [PDF]

				D. C.-l. Lam, L. Girard, R. Ramirez, W.-s. Chau, W.-s. Suen, S. Sheridan, V. P.C. Tin, L.-p. Chung, M. P. Wong, J. W. Shay, et al. Expression of Nicotinic Acetylcholine Receptor Subunit Genes in Non-Small-Cell Lung Cancer Reveals Differences between Smokers and Nonsmokers Cancer Res., May 15, 2007; 67(10): 4638 - 4647. [Abstract] [Full Text] [PDF]

				C. Bose, H. Zhang, K. B. Udupa, and P. Chowdhury Activation of p-ERK1/2 by nicotine in pancreatic tumor cell line AR42J: effects on proliferation and secretion Am J Physiol Gastrointest Liver Physiol, November 1, 2005; 289(5): G926 - G934. [Abstract] [Full Text] [PDF]

				M. Chu, J. Guo, and C.-Y. Chen Long-term Exposure to Nicotine, via Ras Pathway, Induces Cyclin D1 to Stimulate G1 Cell Cycle Transition J. Biol. Chem., February 25, 2005; 280(8): 6369 - 6379. [Abstract] [Full Text] [PDF]

				F. Lechin, B. van der Dijs, A. E. Lechin, and H. A. Boushey Tianeptine: A New Exploratory Therapy for Asthma Chest, January 1, 2004; 125(1): 348 - 349. [Full Text] [PDF]

				Y. N. Ye, E. S. L. Liu, V. Y. Shin, W. K. K. Wu, J. C. Luo, and C. H. Cho Nicotine Promoted Colon Cancer Growth via Epidermal Growth Factor Receptor, c-Src, and 5-Lipoxygenase-Mediated Signal Pathway J. Pharmacol. Exp. Ther., January 1, 2004; 308(1): 66 - 72. [Abstract] [Full Text] [PDF]

				G. M.M. Videtic, L. W. Stitt, A. R. Dar, W. I. Kocha, A. T. Tomiak, P. T. Truong, M. D. Vincent, and E. W. Yu Continued Cigarette Smoking by Patients Receiving Concurrent Chemoradiotherapy for Limited-Stage Small-Cell Lung Cancer Is Associated With Decreased Survival J. Clin. Oncol., April 15, 2003; 21(8): 1544 - 1549. [Abstract] [Full Text] [PDF]

				P. Song, H. S. Sekhon, Y. Jia, J. A. Keller, J. K. Blusztajn, G. P. Mark, and E. R. Spindel Acetylcholine Is Synthesized by and Acts as an Autocrine Growth Factor for Small Cell Lung Carcinoma Cancer Res., January 1, 2003; 63(1): 214 - 221. [Abstract] [Full Text] [PDF]

				C. Missale, A. Codignola, S. Sigala, A. Finardi, M. Paez-Pereda, E. Sher, and P. Spano Nerve growth factor abrogates the tumorigenicity of human small cell lung cancer cell lines PNAS, April 28, 1998; 95(9): 5366 - 5371. [Abstract] [Full Text] [PDF]