Cancer-Type OATP1B3 mRNA in Extracellular Vesicles as a Promising Candidate for a Serum-Based Colorectal Cancer Biomarker
Cancer-Type OATP1B3 mRNA in Extracellular Vesicles as a Promising Candidate for a Serum-Based Colorectal Cancer Biomarker
复制标题
DOI：
10.1248/bpb.b17-00743
复制
发表时间：
2018-03-01
影响因子：
2
通讯作者：
Furihata, Tomomi
中科院分区：
文献类型：
--
作者：
Morio, Hanae;Sun, Yuchen;Furihata, Tomomi
癌型有机阴离子转运多肽1B 3（Ct-OATP 1B 3）mRNA是肝型OATP 1B 3的变体同种型。由于Ct-OATP 1B 3 mRNA在结直肠癌（CRC）中显示出良好的癌症特异性表达谱，并且其表达水平与CRC预后相关，因此它有可能成为有用的CRC检测和诊断生物标志物。虽然目前仅在组织水平证明了这一潜力，但如果证实CRC衍生的细胞外囊泡（EV）中存在Ct-OATP 1B 3 mRNA，则这些发现可能会增强其作为CRC检测和诊断生物标志物的翻译潜力。因此，本研究旨在证明Ct-OATP 1B 3 mRNA存在于CRC源性EV中，并且可以使用血清标本进行检测。为了研究Ct-OATP 1B 3 mRNA存在于细胞外环境中的可能性，我们从人CRC（HCT 116、HT-29和SW 480）细胞系中分离EV，并制备它们的cDNA。RT-PCR结果显示，Ct-OATP 1B 3 mRNA明显存在于来自人CRC细胞系的EV中。然后，为了进一步探索CRC衍生EV中的Ct-OATP 1B 3 mRNA可以在血清中检测的可能性，我们分离了来自人CRC异种移植小鼠的血清EV，然后进行RT-PCR。结果表明，在所有受检小鼠的血清EV和CRC组织样品中均能检测到Ct-OATP 1B 3 mRNA。总的来说，我们的研究结果表明，Ct-OATP 1B 3 mRNA存在于EV中，并且可以在（至少）小鼠血清中检测到，加强了Ct-OATP 1B 3 mRNA作为基于血清的CRC生物标志物的潜在用途。
Cancer-type organic anion transporting polypeptide 1B3 (Ct-OATP1B3) mRNA is a variant isoform of the liver-type OATP1B3. Because Ct-OATP1B3 mRNA shows an excellent cancer-specific expression profile in colorectal cancer (CRC), and that its expression levels are associated with CRC prognosis, it holds the potential to become a useful CRC detection and diagnosis biomarker. While the potential is currently justified only at the tissue level, if existence of Ct-OATP1B3 mRNA in CRC-derived extracellular vesicles (EVs) is validated, the findings could enhance its translational potential as a CRC detection and diagnosis biomarker. Therefore, this study aims at proving that Ct-OATP1B3 mRNA exists in CRC-derived EVs, and can be detected using serum specimens. To examine the possibility of Ct-OATP1B3 mRNA being existed in extracellular milieu, we isolated EVs from the human CRC (HCT116, HT-29, and SW480) cell lines, and prepared their cDNAs. The RT-PCR results showed that Ct-OATP1B3 mRNA was clearly present in EVs derived from the human CRC cell lines. Then, in order to further explore the possibility that Ct-OATP1B3 mRNA in CRC derived EVs can be detected in serum, we isolated serum EVs derived from human CRC xenograft mice, and then performed RT-PCR. The results showed that Ct-OATP1B3 mRNA could be found in all serum EV and CRC tissue samples of the mice examined. Collectively, our findings, which show that Ct-OATPIB3 mRNA exists in EVs and can be detected in (at least) mouse serum, strengthen the potential use of Ct-OATP1B3 mRNA as a serum-based CRC biomarker.