Mesenchymal Stem Cells (MSCs) are inherently tumour-homing, 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 tumours including gliomas and breast, colon, ovarian, and lung carcinomas, among many other primary and metastatic tumours. 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. Furthermore, we have identified MIF as the major trigger for MSC homing, being secreted from tumour cells at high levels.

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. Importantly, knocking down the expression of CXCR4 in MSCs or MIF in tumour cells, drastically decreased MSC recruitment to tumours in a in vivo model of lung metastasis.

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.