Original ArticleFullerenol inhibits the cross-talk between bone marrow-derived mesenchymal stem cells and tumor cells by regulating MAPK signaling

The interaction between bone marrow-derived mesenchymal stem cells (BDMSCs) and tumor cells promotes tumor proliferation and metastasis. We found that 4T1 breast cancer cells induced malignant differentiation of BDMSCs and that BDMSCs also affected the growth and metastasis of 4T1 cells. However, when the interaction between BDMSCs and 4T1 cells was attenuated or blocked by C60(OH)22 nanoparticles, tumor growth and metastasis were significantly suppressed. The suppression of metastasis depended on the activation of MAPK signals in the BDMSCs, whereas the underlying pathways were related to a broad range of extracellular responses and were modulated by the secretion of multiple cytokines. Interestingly, C60(OH)22 regulated the malignantly differentiated BDMSCs via the Erk- and p38-MAPK and its downstream NF-κB signal pathway, but in normal BDMSCs regulation occurred only through Erk- and p38-MAPK and not by NF-κB activation. This study may provide a novel mechanism for C60(OH)22 nanoparticles as an anti-tumor drug.

Graphical AbstractThe interaction between bone marrow-derived mesenchymal stem cells (BDMSCs) and tumor cells promotes tumor proliferation and metastasis. The fullerenol nanoparticles could attenuate the cytokines secretion of BDMSCs by regulating the MAPK signaling pathway and then inhibit the cross-talk of BDMSCs and tumor cells. The different regulation of normal and malignant BDMSCs makes the fullerenol a potential anti-tumor drug with reduced side effects.242