Characterising the expression of the organic cation transporter OCT3 in cutaneous papillomas of dogs

Abstract

Background: The identification of the activation of the mammalian targetof rapamycin (mTOR) signalling pathway as a frequent molecular event incanine cutaneous papillomas (CPs) has provided the rational foundation toexplore novel molecular-targeted therapies. Recent evidence indicates thatmetformin reduces the size of CPs in mice by inhibiting the mTOR signallingpathway. These effects require the expression of the organic cation transporter 3 (OCT3/SLC22A3), a well-known metformin uptake transporter.Hypothesis/Objectives: The aim of the present study was to characterisethe expression pattern of the metformin uptake transporter OCT3 in caninesamples of CP that have shown activation of the mTOR signalling pathwayin order to predict if this hyperplastic epidermal lesion is potentially sensitiveto metformin.Methods: The expression of OCT3 was evaluated by immunohistochemicalinvestigation in sections of a previously constructed tissue microarray containing 28 samples of canine CP and compared with that previously evaluatedfor the mTOR activation marker pS6. Results: OCT3 was highly expressed in the membrane and cytoplasm ofthe basal and suprabasal epidermal cells in all samples of canine CP. ThisOCT3 expression was localised at similar epidermal compartments to thoseobserved for pS6.Conclusions and Clinical Relevance: These results show that canine CPsexhibit the expression of surrogate markers that suggest sensitivity to metformin, such as upregulated OCT3 and pS6 expression. Taken together, thesefindings provide the rationale for the early assessment of the use of metformin as a mechanism-based therapeutic approach for treating canine patients with persistent or multiple CPs.