Human liver‐specific organic anion transporter‐2 is a potent prognostic factor for human breast carcinoma

Muto, M.; Onogawa, Tohru; Suzuki, Takashi; Ishida, Toru; Rikiyama, Toshiki; Katayose, Yu; Ohuchi, Noriaki; Sasano, Hironobu; Abe, Takaaki; Unno, Michiaki

doi:10.1111/j.1349-7006.2007.00570.x

Cited by 85 publications

(91 citation statements)

References 27 publications

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“…Certain (60) ↑ in prostate cancer cells (6) qRT-PCR Kidney (64) ↑ in bone cancer (65) RT-PCR OATP1B1 Liver (2,66) ↓ in liver cancer (37)(38)(39)67,68) RT-PCR, IF, IB ↑ in colon polyps and colon cancer (63) RT-PCR ↑ in ovarian cancer (69) RT-PCR OATP1B3 Liver (3,70) ↓ in liver cancer (41) qRT-PCR, IB ↑ in colon cancer (4,71,72) RT-PCR, qRT-PCR, IB, IHC ↑ in pancreatic cancer (71)(72)(73) RT-PCR, qRT-PCR, IB, IHC ↑ in lung cancer (38) RT-PCR, qRT-PCR, IF ↑ in prostate cancer (16,17,68,74) qRT-PCR, IF ↑ in breast cancer (75) qRT-PCR, IHC ↑ in testicular cancer (68) qRT-PCR, IF ↑ in ovarian cancer (69) RT-PCR OATP1C1 Brain (76) ↑ in bone cancers (65) RT-PCR Testes (76) Ciliary body (77) OATP2A1 Ubiquitous (78) ↑ in breast cancer (79) qRT-PCR ↑ in liver cancer (80) qRT-PCR, IF ↑ in bone metastases from kidney cancer (65) qRT-PCR, IB ↓ in cancers of bowel, stomach, ovary, lung, and kidney (81) RT-PCR OATP2B1 Blood-brain barrier (82) ↑ in bone cancer (65) RT-PCR Heart (83) ↑ in breast cancers (79,84) qRT-PCR, IF, IB Enterocytes (85) ↓ in liver and pancreatic cancers (68) qRT-PCR Liver (86) Placenta (87) OATP3A1 Ubiquitous (88) ↑ in bone cysts …”

Section: Discussionmentioning

confidence: 99%

“…This finding was subsequently corroborated by multiple studies which utilized RT-PCR and immunohistochemical detection methods (Table II). In human breast cancer, OATP1B3 was detected in approximately 50% of the clinical tissue samples examined by immunohistochemistry and OATP1B3 immunoreactivity was associated with a decreased risk of recurrence and improved prognosis (75). The authors speculated that OATP1B3 overexpression may be associated with hormone-dependent growth mechanisms considering that OATP1B3 transports E3S.…”

Section: Oatp1b3 (Gene Symbol Slco1b3)mentioning

confidence: 99%

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Role of Organic Anion-Transporting Polypeptides (OATPs) in Cancer Therapy

Thakkar

Lockhart

Lee

2015

AAPS J

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Abstract. The superfamily of organic anion-transporting polypeptides (OATPs, gene symbol SLCO) includes important transporters handling a variety of endogenous and xenobiotic substrates. Currently, 11 human OATPs are known and their substrates include endogenous hormones and their conjugates, anticancer drugs, and imaging agents. The contribution of OATPs to the in vivo disposition of these substrates has been extensively investigated. An accumulating body of evidence also indicates that the expression of some OATPs may be up-or downregulated in several types of cancers, suggesting potential pathogenic roles during the development and progression of cancer. Given that the role of OATPs in handling cancer therapeutics has been already covered by several excellent reviews, this review will focus on the recent progresses on the topic, in particular the role of OATPs in the disposition of anticancer drugs, the impact of OATP genetic variations on the function of OATPs, and the OATPs differentially expressed in cancer and their potential roles in cancer development, progression, and treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Oatp1b3 (Gene Symbol Slco1b3)mentioning

confidence: 99%

Role of Organic Anion-Transporting Polypeptides (OATPs) in Cancer Therapy

Thakkar

Lockhart

Lee

2015

AAPS J

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“…OATP1B3, for example, is found in gastric, colon, and pancreatic cancers (22), in breast carcinomas (23), and lung cancer (24). OATP1A2 and OATP2B1 have also been detected in breast tumors (25) and in epithelia of invasive ductal carcinomas of mammary tissue (26), respectively.…”

Section: A B Cmentioning

confidence: 99%

High Impact of Oatp1a/1b Transporters on In Vivo Disposition of the Hydrophobic Anticancer Drug Paclitaxel

Steeg

Esch

Wagenaar

et al. 2011

Clinical Cancer Research

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Purpose: Organic anion-transporting polypeptides (OATP) mediate the cellular uptake of a broad range of drugs. The hydrophobic anticancer drug, paclitaxel (PTX), was recently identified as a substrate for OATP1B3 in vitro. We investigated the role of Oatp1a/1b transporters in the pharmacokinetics of PTX in vivo, as well as their impact at different dose levels of PTX and methotrexate (MTX).Experimental Design: Recently generated Slco1a/1b À/À (lacking all Oatp1a/1b transporters) and wildtype mice were intravenously dosed with 2, 10, or 50 mg/kg of PTX, or with 10, 50, or 500 mg/kg of MTX, and plasma and tissue drug concentrations were measured.Results: In spite of its hydrophobicity, PTX systemic exposure (at 10 mg/kg) was increased by greater than 2-fold in Slco1a/1b À/À mice compared with wild-type, whereas PTX liver uptake was reduced by about 2-fold. Oatp1a/1b transporters displayed a high impact on PTX and MTX pharmacokinetics over a broad dose range. For MTX, even at 500 mg/kg, saturation of Oatp1a/1b was not observed, with a 3.4-fold increase in plasma and 30-fold decrease in liver levels in Slco1a/1b À/À mice compared with wild-type.Although beginning saturation of Oatp1a/1b was observed at the highest dose of PTX, plasma levels in Slco1a/1b À/À mice were still 1.7-fold increased and liver levels 1.5-fold decreased compared with wild-type.Conclusion: Oatp1a/1b transporters play a pronounced role in determining plasma levels and tissue distribution of MTX and PTX, thus affecting even highly hydrophobic drugs. Variation in OATP1A/1B transporter activity, due to genetic variation, inhibition, and/or tumor expression might affect toxicity and therapeutic efficacy of these anticancer drugs.

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“…Among these, SLCO1B3 (also known as LST-2) seems the most interesting, for several reasons. First, overexpression of this gene has been clearly observed in a variety of tumors, including breast, prostate, and gastrointestinal cancers (10,11). Second, this gene has been reported to code for the key methotrexate transporter in colorectal cancer (12).…”

Section: Genes With a Restricted Expression In Normal Tissues And Difmentioning

confidence: 99%

Bioinformatics construction of the human cell surfaceome

Cunha

Galante

Souza

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

117

125

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Cell surface proteins are excellent targets for diagnostic and therapeutic interventions. By using bioinformatics tools, we generated a catalog of 3,702 transmembrane proteins located at the surface of human cells (human cell surfaceome). We explored the genetic diversity of the human cell surfaceome at different levels, including the distribution of polymorphisms, conservation among eukaryotic species, and patterns of gene expression. By integrating expression information from a variety of sources, we were able to identify surfaceome genes with a restricted expression in normal tissues and/or differential expression in tumors, important characteristics for putative tumor targets. A high-throughput and efficient quantitative real-time PCR approach was used to validate 593 surfaceome genes selected on the basis of their expression pattern in normal and tumor samples. A number of candidates were identified as potential diagnostic and therapeutic targets for colorectal tumors and glioblastoma. Several candidate genes were also identified as coding for cell surface cancer/testis antigens. The human cell surfaceome will serve as a reference for further studies aimed at characterizing tumor targets at the surface of human cells.colorectal tumors ͉ CT antigens ͉ glioblastoma ͉ transmembrane ͉ tumor cell surface antigens W ith the availability of the human genome sequence, an important goal of current biological research is a more specific and accurate annotation of human genes. One critical property is the subcellular localization of gene products, because this affects their use as potential diagnostic and therapeutic targets. In this respect, the identification of cell surface proteins is of particular interest (1-3) because these proteins represent ideal therapeutic targets. Indeed, cell surface proteins have proved to be relevant to many areas of medicine, and a number of monoclonal antibodies against them are approved for therapeutic applications by the Food and Drug Administration, particularly in cancer therapy. Furthermore, cell surface proteins are also excellent targets for diagnostic assays, especially in biological fluids. On the other hand, there are several issues that make cell surface proteins difficult to manipulate biochemically. First, their hydrophobic transmembrane (TM) domain makes them insoluble. Second, several posttranslational modifications are not executed in commonly used expression systems. Finally, interactions involving cell surface proteins usually have an extremely short half-life (on the order of milliseconds), which has an effect on the development of purification protocols. Despite these limitations, decades of intensive research of cell surface proteins have generated a significant information base. Ideally, this information should be analyzed in a genome-wide context.We generated here a catalog of more than 3,700 genes believed to encode proteins located at the surface of human cells. For the sake of simplicity, we will call this catalog the ''human cell surfaceome.'' An integrated ...

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Human liver‐specific organic anion transporter‐2 is a potent prognostic factor for human breast carcinoma

Cited by 85 publications

References 27 publications

Role of Organic Anion-Transporting Polypeptides (OATPs) in Cancer Therapy

Role of Organic Anion-Transporting Polypeptides (OATPs) in Cancer Therapy

High Impact of Oatp1a/1b Transporters on In Vivo Disposition of the Hydrophobic Anticancer Drug Paclitaxel

Bioinformatics construction of the human cell surfaceome

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