TIM-3 expression in human osteosarcoma: Correlation with the expression of epithelial-mesenchymal transition-specific biomarkers

Signals from the T cell Ig- and mucin-domain-containing molecules (TIMs) have been demonstrated to be actively involved in regulating the progression of carcinomas. However, the expression and distribution of these molecules in osteosarcoma, the most common primary bone malignancy with poor prognosis, have not been investigated. In this study, the expression of TIMs was examined in nine invasive human osteosarcomas using immunohistochemistry, and the phenotypes were detected by dual immunofluorescence staining. Using immunohistochemistry, it was observed that only TIM-3, rather than TIM-1 or TIM-4, was expressed in these tumor specimens, where it was localized in the cytoplasm and plasma membrane of tumor cells. Dual immunofluorescence staining revealed that the expression of TIM-3 was observed in all cell types investigated, including CD68(+) macrophages, CD31(+) endothelial cells, CK-18(+) epithelial cells and PCNA(+) tumor cells. Notably, in sarcoma cells, TIM-3 was co-expressed with certain biomarkers of epithelial-mesenchymal transition (EMT), including vimentin, Slug, Snail and Smad. These combined results suggest that TIM-3 triggers tumor cells to acquire features of aggressive EMT and may be involved in the pathogenesis of this malignancy.