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 language | English (US) |
|---|---|
| Pages (from-to) | 9184-9193 |
| Number of pages | 10 |
| Journal | Cancer Research |
| Volume | 68 |
| Issue number | 22 |
| DOIs | |
| State | Published - Nov 15 2008 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Serotonin metabolism is dysregulated in cholangiocarcinoma, which has implications for tumor growth. / Alpini, Gianfranco; Invernizzi, Pietro; Gaudio, Eugenio; Venter, Julie; Kopriva, Shelleyko; Bernuzzi, Francesca; Onori, Paolo; Franchitto, Antonio; Coufal, Monique; Frampton, Gabriel; Alvaro, Domenico; Lee, Sum P.; Marzioni, Marco; Benedetti, Antonio; DeMorrow, Sharon.
In: Cancer Research, Vol. 68, No. 22, 15.11.2008, p. 9184-9193.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Serotonin metabolism is dysregulated in cholangiocarcinoma, which has implications for tumor growth
AU - Alpini, Gianfranco
AU - Invernizzi, Pietro
AU - Gaudio, Eugenio
AU - Venter, Julie
AU - Kopriva, Shelleyko
AU - Bernuzzi, Francesca
AU - Onori, Paolo
AU - Franchitto, Antonio
AU - Coufal, Monique
AU - Frampton, Gabriel
AU - Alvaro, Domenico
AU - Lee, Sum P.
AU - Marzioni, Marco
AU - Benedetti, Antonio
AU - DeMorrow, Sharon
PY - 2008/11/15
Y1 - 2008/11/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=56449096956&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=56449096956&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-08-2133
DO - 10.1158/0008-5472.CAN-08-2133
M3 - Article
C2 - 19010890
AN - SCOPUS:56449096956
VL - 68
SP - 9184
EP - 9193
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 22
ER -