Transferrin Receptor-1: Expression in Canine Mammary Tumours and In Vitro Therapeutic Applications

Abstract

The transferrin receptor-1 (TFR-1) is overexpressed in many types of human cancers and, in recent years, several studies have investigated its use as a preferential channel for drug cellular uptake in cancer therapy. In veterinary medicine, TFR-1 expression in cancer cells and tissues has been poorly described, as well as its therapeutic potential. In this study we investigated TFR-1 expression in different subtypes of canine mammary tumours (CMTs) and in two CMT cell lines, one primary (CIPp) and one metastatic (CIPm). Additionally, we also compared the in vitro efficacy of an engineered human apoferritin nanocage loaded with doxorubicin (HFn(DOX)) with the conventional doxorubicin treatment on CIPp and CIPm. In CMT tissues, TFR-1 was more expressed in the tumoral tissues compared to the hyperplastic counterparts, specifically with regards to carcinoma and malignant myoepithelioma and simple carcinoma subtypes (p < 0.05). CIPp and CIPm did not show any significant difference in TFR-1 protein expression, while TFR-1 gene expression was higher in CIPm (p < 0.05). The treatment with HFn(DOX) was more efficient than free doxorubicin only on CIPp at high concentrations (50 μM). In conclusion, we show for the first time the variability of TFR-1 expression in CMT tissues and cell lines. Although further investigations are necessary, HFn can be loaded with different chemotherapeutic compounds, becoming an innovative therapeutic tool for the treatment of cancers highly expressing TFR-1 in veterinary and human medicine.