Human Cancer Biology Expression of Serotonin Receptors in Human Hepatocellular Cancer

Purpose: Serotonin is a well-known neurotransmitter and vasoactive substance. Recent research indicates that serotonin contributes to liver regeneration and promotes tumor growth of human hepatocellular cancer. The aim of this study is to investigate the expression of serotonin receptors in hepatocellular cancer and analyze their potential as a cytotoxic target. Experimental Design: Using a tissue microarray and immunohistochemistry, we analyzed the expressionof serotonin receptors in the liver from176patientswithhepatocellular carcinoma, ofwhichnontumor tissue was available in 109 patients. Relevant clinicopathologic parameters were compared with serotonin receptor expression. Two human hepatocellular cancer cell lines, Huh7 and HepG2, were used to test serotonin antagonists as a possible cytotoxic drug. Results: The serotonin receptors 1B and 2B were expressed, respectively, in 32% and 35% of the patients with hepatocellular cancer. Both receptors were associated with an increased proliferation index, and receptor 1B correlated with the size of the tumor. Serotonin antagonists of receptors 1B and 2B consistently decreased viability and proliferation in Huh7 and HepG2 cell lines. Conclusion: We identified two serotonin receptors that are often overexpressed in human hepatocellular cancer and may serve as a new cytotoxic target. Clin Cancer Res; 18(21); 5902–10. 2012 AACR.