TMIC-42. Overexpression of SLCO1A2 in Glioblastoma and Anaplastic Astrocytoma: Evidence from Immunohistochemistry and Immunocytochemistry

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Abstract High-grade gliomas (HGGs), including glioblastoma and anaplastic astrocytoma, represent some of the most aggressive and treatment-resistant forms of brain tumours in adults. Despite advances, prognosis remains poor largely due to the infiltrative nature of these tumours and the limitations imposed by the BBB on drug delivery. OATPs, particularly SLCO1A2, have emerged as promising targets due to their ability to transport a wide variety of compounds and their upregulation in hypoxic tumour microenvironments. we evaluated the expression of SLCO1A2 in high-grade gliomas using immunohistochemistry (IHC) and immunocytochemistry (ICC). IHC was performed on, paraffin-embedded tumour tissues obtained from over 150 patients diagnosed with HGGs. A panel of antibodies targeting key cellular markers was used to delineate cell types, including CD44 (tumour cells), PDGFRB (stromal cells), IBA1 (myeloid cells), and UEA1 (endothelial cells). These were co-labelled with anti-SLCO1A2 to assess its single-cell expression across these cellular populations. For in vitro validation, ICC was employed on both commercially available and primary human glioma cell lines to determine the expression levels of SLCO1A2 and its potential function. Our IHC results demonstrated strong SLCO1A2 immunoreactivity predominantly in tumour cells marked by CD44, with additional but lower levels of expression observed in the stromal (PDGFRB+) and endothelial (UEA1+) compartments. Notably, the transporter showed minimal colocalization with IBA1+ myeloid cells, suggesting cell-type specificity in its expression. In vitro, ICC analysis revealed high levels of SLCO1A2 expression in all investigated cell lines, with clear localisation to the plasma membrane, indicating its functional readiness to mediate transport of substrates across the cell membrane. We also demonstrated that a reported drug carrier molecule, Heptamethine cyanine dyes (HMCDs), utilised SLCO1A2 to deliver anticancer agents into tumour cells. These findings suggest SLCO1A2 may aid in drug uptake, highlighting its potential as a therapeutic target to improve drug delivery and treatment specificity in malignant gliomas.

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