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DOI: 10.1055/s-0032-1332062
Downregulation of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) in human cholangiocellular carcinoma and their prognostic significance
Introduction: The cholangiocellular carcinoma (CCC) is a primary hepatic malignancy derived from cholangiocytes. The prognosis for CCC is very poor and conventional chemotherapy is not effective in prolonging long-term patient survival rates. The organic cation transporters OCT1 and OCT3 mediate the transport of a broad spectrum of endogenous substrates and the detoxification of xenobiotics. Moreover, OCTs are held responsible for the responsiveness towards platin-containing chemotherapies. No data exist about the relevance of OCTs in CCC. Therefore, the aim of this study was to examine the expression of OCT1 and OCT3 in CCC and the corresponding non neoplastic tumor surrounding tissue (TST).
Methods: OCT1 (SLC22A1) and OCT3 (SLC22A3) mRNA expression was measured in primary human CCC and TST by real time PCR (n=27). Protein expression was determined by western blot analysis and immunohistochemistry. Data were correlated with the clinicopathological parameters of CCC.
Results: Real time PCR showed a downregulation of SLC22A1 and SLC22A3 in CCC compared to TST (p<0.001). A low SLC22A1 expression was associated with a worse patient survival (p<0.05). Downregulation was significantly associated with advanced CCC stages as tumors with low SLC22A1 mRNA expression showed larger diameters (p=0.02). There was no significant difference in tumor characteristics or patients survival according to the level of the SLC22A3 expression. Western blot analysis and immunohistochemistry confirmed downregulation of OCT1 and OCT3 protein in cancerous tissue compared to TST.
Conclusion: The downregulation of OCT1 is associated with tumor progression and a worse patient survival.