Cancer-Type OATP1B3 mRNA in Extracellular Vesicles as a Promising Candidate for a Serum-Based Colorectal Cancer Biomarker

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  • Morio Hanae
    Department of Pharmacology, Graduate School of Medicine, Chiba University Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University
  • Sun Yuchen
    Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University
  • Harada Manami
    Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University
  • Ide Hideyuki
    Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University
  • Shimozato Osamu
    Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute
  • Zhou Xujia
    Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University
  • Higashi Kenjirou
    Department of Pharmaceutical Technology, Graduate School of Pharmaceutical Sciences, Chiba University
  • Yuki Ryuzaburo
    Laboratory of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University
  • Yamaguchi Naoto
    Laboratory of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University
  • Hofbauer Josefina Piñón
    EB House Austria, Research Program for the Molecular Therapy of Genodermatoses, Department of Dermatology, University Hospital of the Paracelsus Medical University Salzburg
  • Guttmann-Gruber Christina
    EB House Austria, Research Program for the Molecular Therapy of Genodermatoses, Department of Dermatology, University Hospital of the Paracelsus Medical University Salzburg
  • Anzai Naohiko
    Department of Pharmacology, Graduate School of Medicine, Chiba University
  • Akita Hidetaka
    Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University
  • Chiba Kan
    Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University
  • Furihata Tomomi
    Department of Pharmacology, Graduate School of Medicine, Chiba University Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University

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<p>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-OATP1B3 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.</p>

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