The modulation of iron metabolism affects the Rhabdomyosarcoma tumor growth in vitro and in vivo

Purpose: Rhabdomyosarcoma (RMS) is an aggressive rare neoplasm that derives from mesenchymal cells, which frequently develops resistance to the current therapies and the formation of metastases. Thus, new therapies are needed. The alteration of iron metabolism in cancer cells was effective in reducing the progression of many tumors but not yet investigated in RMS. Here we investigated the effect of iron modulation in RMS both in vitro and in vivo. Methods: . We first characterized the most used RMS cell lines representing the most common subtypes, embryonal (ERMS, RD cells) and alveolar (ARMS, RH30 cells), for their iron metabolism, analyzing iron related proteins and genes. Then we investigated the effects of both iron overload and chelation strategies in vitro and in vivo . Results: . RMS cell lines expressed iron related proteins, even if at lower levels compared to hepatic cell lines. The treatment with ferric ammonium citrate (FAC, as iron source) and with deferiprone (DFP, as iron chelator), significantly affected the cell viability of RD and RH30. Moreover, iron supplementation (in the form of iron dextran) or iron chelation (in the form of DFP) were also effective in vivo in inhibiting the tumor mass growth both derived from RD and RH30 with iron chelation treatment the most effective one. Conclusions: . All the data suggest that the iron modulation could be a promising approach to overcome the RMS tumor growth.