MIF-CXCR4 as a novel axis for Mesenchymal Stem Cells recruitment to tumours in vivo.. Homo sapiens

MSCs are inherently tumor-homing and immunosuppressive and can be isolated, cultured, expanded, and transduced, making them viable candidates for cell therapy. MSCs can also be useful in allogeneic transplantation because of their immunocompatibility. MSCs have the capacity to home specifically to tumors including gliomas and breast, colon, ovarian, and lung carcinomas, among many other primary and metastatic tumors. Some discrepancies are however present regarding the mechanism and the involvement of molecules/receptors in MSC homing to tumours. We have used in this study a combination of genome expression profiling and cytokine arrays to screen for candidates mediating MSC homing to two different cancer cell lines: A549 and MDAMB231. We found a variety of interleukines and cytokines already described as players in the process, such as IL6, IL8, CCL2. Additionally, from in vitro migration and invasion assays, we show that CXCR4 is a major player in this mechanism being the essential MSC receptor for the process to occur. For the first time, we have identified in this study a novel axis: MIF-CXCR4, showing a physical interaction between them and validating their essential role in vitro and in vivo. A better understanding of MSC homing players towards tumours will help the development of novel strategies in their use as vehicles in cancer cell therapy. Overall design: Total RNA obtained from mesenchymal stem cells up to passage 5 stimulated or not with conditioned medium from MDAMB231 cell line or A549 cell line for 24h