Glioblastoma (GBM) represent the most frequent and lethal form of brain tumors with limited treatment options. GBM microenvironment includes bone marrow derived mesenchymal stem cells (MSC) that home to tumors including GBM, and regulate their malignancy. However, intra tumour heterogeneity may significantly affect the response to stromal cells, as we have shown in the in vitro model of two types of human GBM lines, U87 and U373 cells, when directly co-cultured with MSCs. In GBM/MSC co-cultures the growth rate of MSCs was reduced and MSC cell fusion with GBM cells was observed. The frequency of cell fusion events were dependent of GBM cell phenotypes, line U373 and U87 with more or less mesenchymal genotype characteristics, respectively. The U87 cell line proved more prone to GBM fusion with MSC than the U373 line. GBM/MSC fusion is inducing kinin-B1 receptor (B1R) expression. Higher B1R expression correlated with higher cell fusion potential of U87 cells as opposed to U373 cells, showing lower rate of fusion events. We showed that B1R activation enhanced GBM cells’ invasion. However, the increased expression of selected proteases upon direct co-cultures with MSC also increased U373, but not U87 invasion, nor in MSC, the latter also being more invasive upon co-culturing with either of GBM cells (1). In view of the above and our previous reports, we suggest that the B1R inhibition should be evaluated further as an anti-invasive adjvant therapeutic tool in treatment of GBM patients. In conclusion, here we are addressing the interplay between intra tumour cell autonomous and inter-tumor cell non-autonomous heterogeneity, pointing on on high complexity of tumour microenvironment in vivo. In addition, bradykinin receptors B1R were pointed out as an important molecular switch simultaneously modulating cell fusion and invasion events, induced by MSC direct contact with GBM cells.