Cancer cells are no more considered the only player in the tumor growth, progression and invasion. Solid tumors such as breast cancer, present a complex microenvironment where cancer cells interplay with stroma cells (fibroblasts, pericytes, endothelial cells, inflammatory cells associated with the immune system and mesenchymal stem cells) and extracellular matrix . In particular, mesenchymal stem cells (MSCs) contribute to the tumor progression by modulating the immune surveillance; promoting angiogenesis and metastasis and by interfering with the epithelial-mesenchymal transition (EMT) [2-3]. However, MSCs show a “double-edged sword” behavior since they are also able to inhibit cancer invasion. For this reason, MSCs are potentially useful to act as carrier of tumor-suppressive molecules or drugs in the tumor site . Pharmaceutical companies are facing huge loss of resources due to the unsuccessful outcome of anti-cancer drugs. The drugs pass the preclinical study, but fail due to adverse outcome effects occurring in the patients involved in the clinical stage. The development of more realist 3D in vitro tumor models is an urgent need in order to carry out precise and accurate drug testing and reducing the number of animals in the preclinical study . In this work, we investigated the paracrine interaction between bone marrow derived MSCs and a heterotypic breast cancer microenvironment composed of cancer cells and fibroblasts. The dynamic in vitro model exploits the potential of the LIVEBOX 1 (IVTech, Italy). The cell viability in static and dynamic condition as well as the amount of extracellular vesicles and exosome secreted by the cells in the different conditions are analyzed. Moreover, the difference in the exosome content of single (3D-bmMSCs and 3D-HMF/MDA-MB-231 in separate LIVEBOX 1) and co-culture (3D-bmMSCs and 3D-HMF/MDA-MB-231 cultured in two connected LIVEBOX 1) were analyzed. The dynamic in vitro models developed in this work aims to deeper investigate the still controversial role of MSCs in the tumor progression and invasion.
This work is supported by European Union Framework Programme for Research and Innovation Horizon 2020 under grant agreement nº 668983 — FoReCaST (Forefront Research in 3D Disease Cancer Models as in vitro Screening Technologies) and by BREAST-IT FCT project (PTDC/BTM-ORG/28168/2017).
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