Serotonin metabolism is dysregulated in cholangiocarcinoma, which has implications for tumor growth

Gianfranco Alpini, Pietro Invernizzi, Eugenio Gaudio, Julie Venter, Shelleyko Kopriva, Francesca Bernuzzi, Paolo Onori, Antonio Franchitto, Monique Coufal, Gabriel Frampton, Domenico Alvaro, Sum P. Lee, Marco Marzioni, Antonio Benedetti, Sharon DeMorrow

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Cholangiocarcinoma is a devastating cancer of biliary origin with limited treatment options. Symptoms are usually evident after blockage of the bile duct by the tumor, and at this late stage, they are relatively resistant to chemotherapy and radiation therapy. Therefore, it is imperative that alternative treatment options are explored. We present novel data indicating that the metabolism of serotonin is dysregulated in cholangiocarcinoma cell lines, compared with normal cholangiocytes, and tissue and bile from cholangiocarcinoma patients. Specifically, there was an increased expression of tryptophan hydroxylase 1 and a suppression of monoamine oxidase A expression (enzymes responsible for the synthesis and degradation of serotonin, respectively) in cholangiocarcinoma. This resulted in an increased secretion of serotonin from cholangiocarcinoma and increased serotonin in the bile from cholangiocarcinoma patients. Increased local serotonin release may have implications on cholangiocarcinoma cell growth. Serotonin administration increased cholangiocarcinoma cell growth in vitro, whereas inhibition of serotonin synthesis decreases tumor cell growth both in vitro and in vivo. The data presented here represent the first evidence that serotonin metabolism is dysregulated in cholangiocarcinoma and that modulation of serotonin synthesis may represent an alternative target for the development of therapeutic strategies.

Original languageEnglish (US)
Pages (from-to)9184-9193
Number of pages10
JournalCancer Research
Volume68
Issue number22
DOIs
StatePublished - Nov 15 2008
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Alpini, G., Invernizzi, P., Gaudio, E., Venter, J., Kopriva, S., Bernuzzi, F., Onori, P., Franchitto, A., Coufal, M., Frampton, G., Alvaro, D., Lee, S. P., Marzioni, M., Benedetti, A., & DeMorrow, S. (2008). Serotonin metabolism is dysregulated in cholangiocarcinoma, which has implications for tumor growth. Cancer Research, 68(22), 9184-9193. https://doi.org/10.1158/0008-5472.CAN-08-2133