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

Biol Pharm Bull. 2018;41(3):445-449. doi: 10.1248/bpb.b17-00743.

Abstract

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.

Keywords: SLCO1B3; cancer biomarker; colorectal cancer; extracellular vesicle; organic anion transporting polypeptide 1B3.

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics*
  • Cell Line, Tumor
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / diagnosis
  • Extracellular Vesicles / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Transplantation
  • Prognosis
  • RNA, Messenger / blood*
  • RNA, Messenger / genetics*
  • RNA, Neoplasm / blood*
  • RNA, Neoplasm / genetics*
  • Real-Time Polymerase Chain Reaction
  • Solute Carrier Organic Anion Transporter Family Member 1B3 / biosynthesis
  • Solute Carrier Organic Anion Transporter Family Member 1B3 / genetics*

Substances

  • Biomarkers, Tumor
  • RNA, Messenger
  • RNA, Neoplasm
  • SLCO1B3 protein, human
  • Solute Carrier Organic Anion Transporter Family Member 1B3