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The Modulation of Melatonin in Tumor-Bearing Animals: Underlying Mechanisms and Possible Significance for Prognosis

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The Pineal Gland and Cancer

Abstract

Earlier clinical studies showed that circulating melatonin is depressed in patients with primary tumors of different histological types including endocrine-dependent (mammary, endometrial, prostate) as well as endocrine-independent (lung, gastric) malignancies. The depression of circulating melatonin is most pronounced in patients with advanced localized primary tumors, where a negative correlation with the size of the tumor is found. In contrast, patients with a high risk to develop breast cancer or with early stages of prostate cancer show a very pronounced secretion of melatonin. Also a considerable number of patients with ovarian cancer exhibit a high melatonin production. The underlying mechanisms involved in the modulation of circulating melatonin in cancer patients is poorly understood and therefore studies on experimental tumor-bearing animals were performed in order to better understand this phenomenon.

Most studies have been carried out in relation to breast cancer using 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary cancers as well as serial transplants derived thereof. These experiments demonstrate that nocturnal circulating melatonin is modulated due to the presence of different types and stages of these experimental tumors, as has been observed for the respective human tumors underlining the relevance of these studies. Rats with chemically induced mammary tumors and slow-growing as well as well-differentiated serial transplants containing epithelial cell elements (adenocarcinomas and carcinosarcomas) have an enhanced production of melatonin involving activation of the rate-limiting enzyme of pineal melatonin biosynthesis (serotonin-N-acetyltransferase). This is probably due to an elevation of the sympathetic tone in response to a stimulation of the cellular immune system during malignant growth. In contrast, nocturnal circulating melatonin is depleted in animals with fast-growing mammary tumor transplants when myoepithelial-mesenchymal conversion leads to pure sarcomas. The depletion of melatonin appears to be due to either a reduced availability of the precursor amino acid tryptophan because of a glucocorticoid-induced activation of the hepatic enzyme tryptophan 2,3-dioxygenase or a direct peripheral degradation of melatonin via indolamine 2,3-dioxygenase expressed in tumor and/or other tissues. The significance of these findings is discussed in terms of a possible extrapolation to the clinical situation as well as to increase our theoretical knowledge concerning the mechanisms involved in complex host-tumor interactions within the framework of the neuroimmunoendocrine network.

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  1. Hella Bartsch
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  2. Christian Bartsch
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  3. Dieter Mecke
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Editors and Affiliations

  1. Centre for Research in Medical and Natural Sciences, University of Tübingen, Ob dem Himmelreich 7, Tübingen, 72074, Germany

    Christian Bartsch  & Hella Bartsch  & 

  2. Laboratory of Experimental Neuroendocrinology/Oncology, Bassett Research Institute, One Atwell Road, Cooperstown, NY, 13326, USA

    David E. Blask Ph.D.,M.D. (Senior Research Scientist) (Senior Research Scientist)

  3. Department of Physiology Faculty of Medicine, University of Buenos Aires, Paraguay 2155, Buenos Aires, 121, Argentina

    Daniel P. Cardinali M.D.,Ph.D.

  4. WJB Dorn VA Medical Center, University of South Carolina, 6439 Garners Ferry Road, Columbia, SC, 29209, USA

    William J. M. Hrushesky M.D. (Director of Research (151) (Director of Research (151)

  5. Institute of Physiological Chemistry, University of Tübingen, Hoppe-Seyler-Str. 4, Tübingen, 72076, Germany

    Dieter Mecke (Director) (Director)

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Bartsch, H., Bartsch, C., Mecke, D. (2001). The Modulation of Melatonin in Tumor-Bearing Animals: Underlying Mechanisms and Possible Significance for Prognosis. In: Bartsch, C., Bartsch, H., Blask, D.E., Cardinali, D.P., Hrushesky, W.J.M., Mecke, D. (eds) The Pineal Gland and Cancer. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59512-7_8

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  • DOI: https://doi.org/10.1007/978-3-642-59512-7_8

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