Abstract
The tumor microenvironment, including stromal cells, surrounding blood vessels and extracellular matrix components, has been defined as a crucial factor that influences the proliferation, drug-resistance, invasion and metastasis of malignant epithelial cells. Among other factors, the communications and interaction between cancer cells and stromal cells have been reported to play pivotal roles in cancer promotion and progression. To investigate these relationships, an on-chip co-culture model was developed to study the cellular interaction between A549—human lung carcinoma cells and MRC-5—human lung epithelial cells in both normal proliferation and treatment conditions. In brief, a co-culture device consisting of 2 individual fluidic chambers in parallel, which were separated by a 100 μm fence was utilized for cell patterning. Microelectrodes arrays were installed within each chamber including electrodes at various distances away from the confrontation line for the electrochemical impedimetric sensing assessment of cell-to-cell influence. After the fence was removed and cell-to-cell contact occurred, by evaluating the impedance signal responses representing cell condition and behavior, both direct and indirect cell-to-cell interactions through conditioned media were investigated. The impact of specific distances that lead to different influences of fibroblast cells on cancer cells in the co-culture environment was also defined.
Highlights
There is growing evidence demonstrating that the tumor microenvironment, including stromal cells, inflammatory cells, extracellular matrix (ECM), cytokines, vessels and growth factors, plays an important role in the initiation, progression and invasion of cancer [1,2,3]
We proposed a simple co-culture model with embedded high-throughput microelectrode arrays (MEA) using an electric cell-substrate impedance sensing (ECIS) assay (Fig 1) to monitor tumor cell conditions continuously when confronted with cultured fibroblasts
MEA characterization via monocultures of tumor cells and fibroblasts In the first experimental step, the MEA cell chips were validated via monocultures of A549 tumor cells and MRC-5 fibroblasts in normal proliferative conditions
Summary
There is growing evidence demonstrating that the tumor microenvironment, including stromal cells, inflammatory cells, extracellular matrix (ECM), cytokines, vessels and growth factors, plays an important role in the initiation, progression and invasion of cancer [1,2,3]. Cancer cells interact dynamically with surrounding stromal cells, such as fibroblasts, adipose cells and resident immune cells. Fibroblasts form the largest group of stromal cells and appear to function prominently in cancer progression [4,5]. First described in the late 19th century, fibroblasts are elongated, non-vascular, non-epithelial and non-inflammatory cells of the connective tissue with extended cell processes that show. ECIS in Cancer - Fibroblast Interaction Study
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