Abstract 3530: OATP1B3 in pancreatic cancer tissue as a potential target for anticancer drug transport

Abstract

Abstract Organic Anion Transporting Polypeptides (OATPs) are multispecific transporters that are expressed in normal and cancerous tissue (e.g. colon, prostate, breast and bone cancers). Several anticancer drugs have been shown to be transported by certain OATPs. The aim of the study was to determine the expression of OATPs in pancreatic cancer tissue and functionally characterize anticancer drug transport via the expressed OATPs. Ten pancreas tissue samples were obtained for analysis: 6 normal pancreas, 3 pancreatic cancer and 1 metastatic tissue. Expression of OATPs was analyzed at the mRNA level using the Quantigene assay. Protein expression and localization were determined by immunofluorescence with OATP specific antibodies. Transport of the radiolabeled anticancer drugs paclitaxel and docetaxel was measured in an OATP-expressing Chinese Hamster Ovary (CHO) cell system. Among the 11 human OATPs, expression in pancreatic cancer tissue at the mRNA level was highest for OATP4A1 followed by OATP3A1, OATP2A1 and OATP1B3. Expression of OATP4A1, OATP3A1 and OATP1B3 was confirmed at the protein level. In addition, transport of paclitaxel and docetaxel was observed in OATP1B3-expressing CHO cells with Km values of 2.2 μM for both substrates. In summary, OATP4A1, OATP3A1 and OATP1B3 are expressed in pancreatic cancer. OATP1B3 transports the anticancer drugs paclitaxel and docetaxel with relatively high affinities. In conclusion, given that OATP1B3 is exclusively expressed in normal human hepatocytes, which are generally resistant to the effects of anticancer therapy, transport of anticancer drugs via this transporter might be a feasible approach to target the killing of OATP1B3-expressing cancer cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3530.