MCF7-MSC co-culture assay: approach to assess the co-operation between MCF-7s and MSCs in tumor-induced angiogenesis

The multipotent stromal cells (MSCs) exhibit a broad differentiation potential. MSCs might participate in neovascularization through their ability to migrate and generate capillary-like structures. These processes were shown to be modulated by tumor angiogenic factors, such as Vascular Endothelial Growth Factor (VEGF). The aim of our study was to define the way the MCF-7 cell line (MCF-7s) influenced the MSCs’ recruitment for the tumor-induced angiogenesis, and to assess the role of VEGF in this process. We tested the chemotactic potential of plasma or VEGF, but also of MCF-7s or their conditioned medium (CM) in the MSCs’ transmigration. We compared the migratory potential of MSCs, MSCEs (MSCs cultured in endothelial cell growth medium) and HUVECs. Recombinant VEGF has been shown to chemoattract MSCs, although to a lesser degree than plasma or serum containing medium alone. Moreover, it changed the MSCs’ morphology, stimulating the appearance of longer and thinner prolongations as compared to plasma. MCF-7s or their CM both directly induced migration of MSCs. Surprisingly, CM augmented with MCF-7s attracted less cells than the control medium itself, but CM augmented or not with MCF-7s changed the morphology of MSCs in a manner similar to VEGF. The migratory behavior of the MSCEs was comparable to that of HUVECs, while their morphology could be considered intermediate between MSCs and HUVECs, as they developed shorter prolongations than MSCs, but much longer than HUVECs in the corresponding wells. In conclusion, both tumor cells and VEGF alter the migration behavior of MSCs in a transmigration model, indicating a role of tumor cell-derived VEGF to modulate the recruitment of MSCs into sites of angiogenesis.