Cancer disease is the results of the interplay among cancer cells, fibroblasts, endothelial and immune system cells . The role of mesenchymal stem cells (MSCs) in breast cancer progression is still under debate. In some cases, MSCs are able to trigger tumor progression by modulating the immune surveillance, promoting angiogenesis and metastasis and by interfering with the epithelial-mesenchymal transition (EMT) . MSCs show a “double-edged sword” behavior since they are also able to inhibit cancer invasion . The development of more realist 3D in vitro tumor models is an urgent need in order to understand the role of MSCs in cancer .
In this work, we investigate the paracrine interaction between bone marrow derived MSCs (bmMSCs) and a heterotypic breast cancer microenvironment composed of cancer cells and fibroblasts using a dynamic millifluidic system.
Two chambers of a millifluidic dynamic reactor (LIVEBOX 1, IVTech, Italy) are serially connected to a peristaltic pump. The cell viability in static and dynamic condition are analyzed. Moreover, the differences 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 in two connected LIVEBOX 1) are analyzed both in static and dynamic conditions. Finally, the expression of genes related to the extracellular matrix remodeling are investigated in static and dynamic conditions for both single and co-cultured systems.
The result shows a modulation of exosome-related protein in the different conditions. This also modulates the expression of the genes related to the extracellular matrix remodeling. The dynamic in vitro model developed in this work unravel the role of MSCs in the tumor progression.
This work is supported by H2020 FoReCaST (grant 668983) and by BREAST-IT FCT project (PTDC/BTM-ORG/28168/2017).
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