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Organic Anion Transporting Polypeptides Expressed in Pancreatic Cancer May Serve As Potential Diagnostic Markers and Therapeutic Targets for Early Stage Adenocarcinomas

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ABSTRACT

Purpose

Organic Anion Transporting Polypeptides (OATPs) are expressed in various epithelial tissues in the body. Because they can be expressed in cancers and because they can transport anticancer drugs, OATPs could be potential targets for cancer therapy. Therefore we examined their expression in human pancreatic ductal adenocarcinomas.

Methods

Expression of all 11 human OATPs was measured at the mRNA level and OATPs with highest expression were characterized at the protein level.

Results

Transcripts of SLCO1B3, SLCO2A1, SLCO3A1 and SLCO4A1 were detected in all the tested pancreatic tissues. OATP1B3, OATP2A1, OATP3A1 and OATP4A1 protein expression was confirmed in these tissues and expression of all four transporters increased in pancreatic adenocarcinoma compared to normal pancreas. OATP1B3 expression was highest in pancreatic hyperplasia and stage one adenocarcinomas compared to stage two and three adenocarcinomas.

Conclusion

OATP1B3, OATP2A1, OATP3A1 and OATP4A1 are up-regulated in pancreatic adenocarcinoma and could potentially be used to target anticancer drugs to pancreatic cancer. Additionally, because expression of OATP1B3 is highest in pancreatitis and stage one adenocarcinoma, which leads to pancreatic cancer, OATP1B3 is a potential marker to diagnose patients with early stage pancreatic adenocarcinomas.

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Abbreviations

ABC:

ATP-binding cassette

ADM:

acinar to ductal metaplasia

CAII:

carbonic anhydrase II

MDR:

multidrug resistance

OATP:

organic anion transporting polypeptide

SLCO:

solute carrier family of the OATPs

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ACKNOWLEDGEMENTS AND dISCLOSURES

The authors would like to acknowledge the National Institutes of Health grants: RR021940, GM077336, T32-ES07079, the Ruppenthal Medical Cancer Research Endowment Fund and the University of Kansas Cancer Center Biospecimen Resources for their support.

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Authors and Affiliations

  1. Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, Kansas, 66160, USA

    Amanda Hays, Udayan Apte & Bruno Hagenbuch

  2. The University of Kansas Cancer Center, Kansas City, Kansas, USA

    Bruno Hagenbuch

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  1. Amanda Hays
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  2. Udayan Apte
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Correspondence to Bruno Hagenbuch.

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Hays, A., Apte, U. & Hagenbuch, B. Organic Anion Transporting Polypeptides Expressed in Pancreatic Cancer May Serve As Potential Diagnostic Markers and Therapeutic Targets for Early Stage Adenocarcinomas. Pharm Res 30, 2260–2269 (2013). https://doi.org/10.1007/s11095-012-0962-7

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