We use a microfluidic cell culture chip equipped with pneumatic microvalves to analyze the paracrine loop between lung cancer cells and fibroblasts. In order to assess the cellular responses in the paracrine loop, we measure the migration speeds of cancer cells and the aspect ratios of fibroblasts which reflect the phenotype of myofibroblasts. With well-controlled interaction sequences between these two types of cells, we verify that the cytokines from cancer cells effectively stimulate the fibroblasts into myofibroblasts. The cytokines from myofibroblasts, rather than fibroblasts, increase the migration speeds of cancer cells. We confirm that the transforming growth factor-β1 (TGF-β1) is involved in the interaction between cancer cells and fibroblasts, and we also interrupt this paracrine loop in the cell culture chip by inhibiting the TGF-β1 receptors on fibroblasts.
Using a cell culture chip with a deformable substrate driven by a hydraulic force, we investigated the motility of cancer cells affected by myofibroblasts undergoing cyclic tensile strain (CTS). CTS reduced both the expression of α-smooth muscle actin in the myofibroblast and the ability of the myofibroblast to accelerate cancer cell migration. However, with the treatment of a pro-inflammatory factor interleukin-1β on the myofibroblasts, the effects of CTS on the myofibroblast were diminished. This result suggests an antagonism between mechanical and chemical stimulations on mediating cancer metastasis by the stromal myofibroblast.
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