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.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Alpini G,Invernizzi P,Gaudio E,Venter J,Kopriva S,Bernuzzi F,Onori P,Franchitto A,Coufal M,Frampton G,Alvaro D,Lee SP,Marzioni M,Benedetti A,DeMorrow Sdoi
10.1158/0008-5472.CAN-08-2133subject
Has Abstractpub_date
2008-11-15 00:00:00pages
9184-93issue
22eissn
0008-5472issn
1538-7445pii
68/22/9184journal_volume
68pub_type
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