Mesenchymal stem cell-tumor cell cooperation in breast cancer vasculogenesis

Abstract

Mesenchymal stem cells (MSCs) are able to acquire endothelial-like characteristics but their involvement in regulating MSC vasculogenesis is more complex. MSCs are able to express endothelial markers when cultured in endothelial growth medium (EGM), proving their differentiation into endothelial-like cells. The aim of our study was to evaluate the capacity of the MCF-7 breast cancer cell line to stimulate the organization of regular MSCs and MSCs culture-expanded in EGM (MSCEs) into capillary-like structures and to assess the involvement of tumor-derived VEGF. We seeded MSCs and MSCEs on Matrigel in a Transwell two compartment culture system in the presence of VEGF, MCF-7 cells or their conditioned medium (CM). Both MSCs and MSCEs were CD31-negative, either in culture conditions, or in the Transwell system. MSCs had a clear tendency to organize in clusters and to form capillary-like structures, in the presence of VEGF or MCF-7 cells. MSCEs had a similar behavior, but their tendency to organize in clusters was lower. Neither MSCs nor MSCEs organized into capillary-like structures in the presence of MCF-7 CM, yet the tendency to organize in clusters was stronger in the MSCs. Following exposure both to EGM-2 alone and to EGM-2 supplemented with MSCs or MSCEs, the MCF-7 cells were present as adherent cells on the bottom of the lower wells, while the tendency to organize as single cells (and not in clusters) was more evident when MCF-7 cells were co-cultured with MSCs compared to the other conditions. Both breast cancer cells and VEGF stimulate MSCs and MSCEs to form capillary-like structures, indicating a role of tumor-derived VEGF in modulating their recruitment into sites of pathological vasculogenesis. Preconditioning MSCs in EGM influenced their pattern of organization into capillary-like structures, but the potential changes in the molecular marker profile for their 'switch' to the endothelial cell line remain to be evaluated.