Osteosarcoma (OS) is an aggressive malignancy characterized by a high relapse rate despite multiagent chemotherapy. As for other cancers, OS microenvironment contributes to tumor initiation, growth, and metastasis. We consider bone marrow mesenchymal stromal cells (MSC) as a major nontumor component of OS microenvironment, and have previously found that the interaction between MSC and tumor cells is bidirectional, i.e. tumor cells can modulate their peripheral environment that, in turn, becomes more favourable to tumor growth through metabolic reprogramming (1). Here, we determined the effects of MSC on OS stemness and migration, two major features associated with an increased tendency to relapse and chemoresistance. The presence of MSC enhanced the number of floating spheres enriched in cancer stem cells (CSC) of the OS cell population. Furthermore, co-culturing with MSC stimulated the migratory capacity of OS via IL-6 secretion, and this effect was impaired by the neutralizing antibody Tocilizumab. Thus, MSC and OS-CSC exploit a vicious cycle in which the presence of CSC stimulates MSC cytokine secretion, in turn increasing stemness, proliferation, migration, and metastatic potential of CSC. Furthermore, for the first time, we identified Met, an oncogene that we have observed frequently expressed in aggressive OS (2), and found relevant for the pathogenesis of this tumor (3), as a novel stem cell marker. Altogether, our data highlight the need for a comprehensive knowledge of the interplay between tumor and stroma, that also includes the stem-like fraction of tumour cells, in order to develop novel and more effective anti-cancer therapies.
1. Oncotarget. 2015 6 3045330471.
2. Oncogene. 1995 10 739749.
3. Cancer Res. 2006 66 47504757.
14 May 2016 - 17 May 2016