Organic Anion Transporting Polypeptide 5A1 (OATP5A1) in Small Cell Lung Cancer (SCLC) Cells: Possible Involvement in Chemoresistance to Satraplatin

Olszewski-Hamilton, Ulrike; Svoboda, Martin; Thalhammer, Theresia; Buxhofer‐Ausch, Veronika; Geißler, Klaus; Hamilton, Gerhard

doi:10.4137/bic.s7151

Cited by 15 publications

(14 citation statements)

References 30 publications

(59 reference statements)

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“…Immunohistochemical analyses confirmed that OATP5A1 is expressed on the membrane and in the cytoplasm of breast cancer cells (89). OATP5A1 at both the mRNA and protein levels was found to be upregulated in liver cancer (80) and small cell lung cancer (SCLC) (5). As a potential marker of chemotherapy resistance, HEK-293 cells transfected with OATP5A1 showed resistance to satraplatin treatment (5).…”

Section: Oatp5a1 (Gene Symbol Slco5a1)mentioning

confidence: 83%

“…OATP5A1 at both the mRNA and protein levels was found to be upregulated in liver cancer (80) and small cell lung cancer (SCLC) (5). As a potential marker of chemotherapy resistance, HEK-293 cells transfected with OATP5A1 showed resistance to satraplatin treatment (5). Further studies may be warranted to elucidate the impact of OATP5A1 on tumor resistance and better understand the role OATP5A1 in cancer.…”

Section: Oatp5a1 (Gene Symbol Slco5a1)mentioning

confidence: 99%

“…Subsequent reports revealed that the expression of OATPs may be altered in different disease conditions including cancer and may play a potential role in the development and progression of cancer as well as the disposition of anticancer drugs (2)(3)(4)(5)(6). Given that the role of OATPs in handling cancer therapeutics has been already covered by several excellent reviews (7)(8)(9)(10), this review will focus on the recent findings in the field.…”

Section: Introductionmentioning

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: Oatp5a1 (Gene Symbol Slco5a1)mentioning

confidence: 83%

Section: Oatp5a1 (Gene Symbol Slco5a1)mentioning

confidence: 99%

Section: Introductionmentioning

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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“…There is some evidence that OATP5A1 is involved in the chemoresistance to the oral anticancer drug satraplatin [15]. …”

Section: The Oatp Family Of Transportersmentioning

confidence: 99%

Tumor-Specific Expression of Organic Anion-Transporting Polypeptides: Transporters as Novel Targets for Cancer Therapy

Buxhofer‐Ausch

Secky

Wlcek

et al. 2013

Journal of Drug Delivery

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Members of the organic anion transporter family (OATP) mediate the transmembrane uptake of clinical important drugs and hormones thereby affecting drug disposition and tissue penetration. Particularly OATP subfamily 1 is known to mediate the cellular uptake of anticancer drugs (e.g., methotrexate, derivatives of taxol and camptothecin, flavopiridol, and imatinib). Tissue-specific expression was shown for OATP1B1/OATP1B3 in liver, OATP4C1 in kidney, and OATP6A1 in testis, while other OATPs, for example, OATP4A1, are expressed in multiple cells and organs. Many different tumor entities show an altered expression of OATPs. OATP1B1/OATP1B3 are downregulated in liver tumors, but highly expressed in cancers in the gastrointestinal tract, breast, prostate, and lung. Similarly, testis-specific OATP6A1 is expressed in cancers in the lung, brain, and bladder. Due to their presence in various cancer tissues and their limited expression in normal tissues, OATP1B1, OATP1B3, and OATP6A1 could be a target for tumor immunotherapy. Otherwise, high levels of ubiquitous expressed OATP4A1 are found in colorectal cancers and their metastases. Therefore, this OATP might serve as biomarkers for these tumors. Expression of OATP is regulated by nuclear receptors, inflammatory cytokines, tissue factors, and also posttranslational modifications of the proteins. Through these processes, the distribution of the transporter in the tissue will be altered, and a shift from the plasma membrane to cytoplasmic compartments is possible. It will modify OATP uptake properties and, subsequently, change intracellular concentrations of drugs, hormones, and various other OATP substrates. Therefore, screening tumors for OATP expression before therapy should lead to an OATP-targeted therapy with higher efficacy and decreased side effects.

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“…OATP1A2, 1B1, 1B3 and 2B1 transport a wide range of compounds, from bile acids and hormones, to various therapeutics including statins, antiviral agents and antibiotics. Conversely, OATP3A1, 1C1, 2A1, 4A1, 4C1 and 5A1 have been documented to transport only a few compounds [4, 6, 7]. Currently, there is no published information on the function or substrate specificity of OATP6A1, primarily due to the lack of convenient expression systems and functional assays.…”

Section: Introductionmentioning

confidence: 99%

Functional expression of the 11 human Organic Anion Transporting Polypeptides in insect cells reveals that sodium fluorescein is a general OATP substrate

Patik

Kovacsics

Német

et al. 2015

Biochemical Pharmacology

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Organic Anion Transporting Polypeptides (OATPs), encoded by genes of the Solute Carrier Organic Anion (SLCO) family, are transmembrane proteins involved in the uptake of various compounds of endogenous or exogenous origin. In addition to their physiological roles, OATPs influence the pharmacokinetics and drug-drug interactions of several clinically relevant compounds. To examine the function and molecular interactions of human OATPs, including several poorly characterized family members, we expressed all 11 human OATPs at high levels in the baculovirus-Sf9 cell system. We measured the temperature- and inhibitor-sensitive cellular accumulation of sodium fluorescein and fluorescein-methotrexate, two fluorescent substrates of the OATPs, OATP1B1 and 1B3. OATP1B1 and 1B3 were functional in Sf9 cells, showing rapid uptake (t1/2(fluorescein-methotrexate) 2.64 and 4.16 min, and t1/2(fluorescein) 6.71 and 5.58 min for OATP1B1 and 1B3, respectively) and high-affinity transport (Km(fluorescein-methotrexate) 0.23 and 0.53 μM, and Km(fluorescein) 25.73 and 38.55 μM for OATP1B1 and 1B3, respectively) of both substrates. We found that sodium fluorescein is a general substrate of all human OATPs: 1A2, 1B1, 1B3, 1C1, 2A1, 2B1, 3A1, 4A1, 4C1, 5A1 and 6A1, while fluorescein-methotrexate is only transported by 1B1, 1B3, 1A2 and 2B1. Acidic extracellular pH greatly facilitated fluorescein uptake by all OATPs, and new molecular interactions were detected (between OATP2B1 and Imatinib, OATP3A1, 5A1 and 6A1 and estradiol 17-β–D-glucuronide, and OATP1C1 and 4C1 and prostaglandin E2). These studies demonstrate for the first time the applicability of the insect cell system for the functional expression of the entire human OATP family, and for drug-OATP interaction screening.

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Organic Anion Transporting Polypeptide 5A1 (OATP5A1) in Small Cell Lung Cancer (SCLC) Cells: Possible Involvement in Chemoresistance to Satraplatin

Cited by 15 publications

References 30 publications

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

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

Tumor-Specific Expression of Organic Anion-Transporting Polypeptides: Transporters as Novel Targets for Cancer Therapy

Functional expression of the 11 human Organic Anion Transporting Polypeptides in insect cells reveals that sodium fluorescein is a general OATP substrate

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