Relationships between transferrin and transferrin receptor (TfR) expression in dogs with malignant oronasal tumors

Malignant cells require a large amount of iron for cell growth. Transferrin transfers iron from blood to cells by reacting with transferrin receptor (TfR). In humans, transferrin and transferrin receptor correlate with oral squamous cell carcinoma (OSCC); however, the association with canine oral tumor has not been studied. This study aimed to investigate saliva and serum transferrin and tissue transferrin receptor in canine OSCC and oral melanoma (OM). Saliva and serum transferrin samples were collected pre- and 14 days post-operation, compared with healthy control and evaluated by a sandwich ELISA assay. Serum transferrin concentration in the experimental group both before and after surgery was significantly lower than that in the normal group (p < 0.05). However, no significant difference in serum transferrin levels before and after surgery was observed. Saliva transferrin expression of the dogs with oronasal cancer before surgical treatment tended to be higher than that of the control group. In contrast, at post-operation, they were not significantly different. Dogs with clinical stage I oronasal cancer revealed the highest saliva transferrin level as in humans. In addition, transferrin receptor expression, evaluated by immunohistochemistry, in the dogs with oronasal cancer was higher than that in the control group (p < 0.001). The decrease in serum transferrin was probably due to the uptake of transferrin bound iron by cancer cells. In conclusion, this study demonstrated the new role of transferrin and its receptor for iron acquisition in canine OSCC and OM.