5). Blood vessels were stained with an anti-CD34 antibody and the cell nuclei www.selleckchem.com/products/CP-690550.html were visualized by counterstaining with bisbenzimide. An overlay of the different fluorescences revealed OATP5A1-staining preferentially in the cytoplasm and near the cell membrane in the majority of the cells. Figure 5 Immunohistochemical staining of an SCLC with anti-OATP5A1 antibody. The paraffin-embedded SCLC specimen was stained with anti-OATP5A1 and anti-CD34 antibodies, which recognizes blood vessels (top left). Cell nuclei are shown in blue due to counterstaining … Discussion Gene expression analyses of human tissue samples indicated absence of SLCO1A2 and the two liver-specific SLCOs 1B1 and 1B3, as well as 1C1, 5A1 and 6A1 in the lungs.21 However, SLCOs 2B1, 3A1 and 4A1 were detected in the same tissue, while SLCO4C1 was moderately present.

Normal bronchial cells expressed high levels of SLCOs 3A1 and 4A1.21 Furthermore, respiratory epithelial cells exhibited a weak cytoplasmic/membranous staining with anti-OATP5A1 antibody HPA025062. OATP1B1 and 1B3 are known to mediate the transmembrane transport of paclitaxel, but tumor cells are expected to downregulate their expression to avoid cell death in response to cytotoxic compounds. Other OATPs that are upregulated in tumor cells are likely to participate in mechanisms leading to chemoresistance. Detection of OATP5A1 in U-251 MG glioblastoma and A431 epidermoid carcinoma cells with antibody HPA025062 revealed granular/fibrous staining in the cytoplasm.

The majority of malignant cells were either OATP5A1-negative or displayed weak cytoplasmic staining, with exception of a fraction of ovarian and lung and a large number of renal cancer specimens, which showed moderate to strong cytoplasmic and nuclear Anacetrapib immunoreactivity. Several OATPs, such as human 1A2, 1C1, 2B1, 4A1 and 6A1, possess a C-terminal postsynaptic density-95(PSD-95)/Discs-large/ZO-1 (PDZ) consensus sequence.8,9 Recently it was shown that binding to PSD-95/Discs-large/ZO-1 domain-containing 1 (PDZK1) is essential for plasma membrane incorporation of rat Oatp1a1.23�C25 Thus, a similar mechanism could be responsible for the plasma membrane localization of all OATPs with a C-terminal PDZ consensus sequence. It is therefore suggested that some OATPs may be involved in the intracellular transport of compounds across vesicle membranes instead of facilitating transmembrane cellular drug uptake. According to our own results obtained with HEK-293-SLCO5A1 cells, cisplatin does not serve as a substrate of OATP5A1, since its cytotoxicity is not altered; in contrast, introduction of lipophilic moieties to the basic structure of cisplatin, i.e.