VALUTAZIONE DELL’ESPRESSIONE DEL TFR-1 NEL TUMORE MAMMARIO DI GATTO E CANE E DELLA POSSIBILE EFFICACIA TERAPEUTICA DI UNA NANOCAGE IN COLTURE CELLULARI DI TUMORE MAMMARIO DI CANE E GATTO

The transferrin receptor (TFR-1) has been found to be overexpressed in several solid tumors in humans and, in clinical oncology, has therefore been exploited in a selective anticancer therapy using nanotechnology. The ferritin (HFn), a molecule able to recognize TFR-1, was used to create a nanocage loaded with doxorubicin HFn(DOX). In veterinary medicine there are few studies that evaluate the expression of TFR-1 in tumors especially in mammary cancer and, even fewer are the studies that use it for therapy. The goal of this study is therefore the evaluation of TFR-1 expression in malignant mammary tumors of cats and dogs, either in tumor tissues and in cancer cell lines, and additionally to demonstrate the efficacy of HFn(DOX) in feline and canine mammary tumor cell lines. Interestingly, on tumor sections of different degrees of malignancy, we observed that in cats, the level of TFR-1 protein expression increases with the progression of malignancy, while in the dog a greater expression of the receptor has been identified on tumor sections compared to healthy mammary gland. As regards to the efficacy of the use of HFn(DOX), in feline metastatic mammary cancer cells line, a lower cell proliferation has been observed compared to the administration of the drug alone, at specific concentrations and time points (specifically 0.01 µM after 72 hours from treatment and 0.1 µM after 48 and 72 hours). In dogs, on the other hand, HFn(DOX) was effective only in tumor cells derived from a primary cancer at higher concentrations (5 µM and 12.08 µM after 72 hours) than those used in the cats. Apparently then, canine mammary cancer cells resulted more resistant to doxorubicin than the counterpart in cats, as in the dog it was necessary to use higher concentrations of drug either linked to the nanocage and free. The results of this preliminary study confirmed the presence of the TFR-1 in the mammary tumor of cats and dogs, highlighting a correlation of its expression with the degree of tumor malignancy in particular in the cat, suggesting that the use of engineered nanomolecules could be an effective therapeutic option for mammary cancer in this animal species. For the dog, further studies are mandatory, including more cell lines, or using the nanocage loaded with other drugs. In conclusion, the study demonstrated that the use of engineered molecules that selectively bind to specific receptors over-expressed on neoplastic cells is a promising field of study for new therapeutic horizons also in veterinary medicine.