Abstract
Fibroblasts have significant involvement in cancer progression and are an important therapeutic target for cancer. Here, we present a microfluidic non-contact co-culture device to analyze interactions between tumor cells and fibroblasts. Further, we investigate myofibroblast behaviors induced by lung tumor cells as responses to gallic acid and baicalein. Human lung fibroblast (HLF) and lung cancer cell line (A549) cells were introduced into neighboring, separated regions by well-controlled laminar flows. The phenotypic behavior and secretion activity of the tumor cells indicate that fibroblasts could become activated through paracrine signaling to create a supportive microenvironment for cancer cells when HLF is co-cultured with A549. Furthermore, both gallic acid (GA) and baicalein (BAE) could inhibit the activation of fibroblasts. In situ analysis of various cell communications via the paracrine pathway could be realizable in this contactless co-culture single device. This device facilitates a better understanding of interactions between heterotypic cells, thus exploring the mechanism of cancer, and performs anti-invasion drug assays in a relatively complex microenvironment.
Highlights
Cancer progression has an affinity relationship with the tumor microenvironment, including the extracellular matrix (ECM), fibroblasts, immune cells, and endothelial cells, and the blood vessels and proteins produced [1,2]
Some researchers compared the effect of normal fibroblasts with that of carcinoma-associated fibroblasts (CAFs) on tumor cells and demonstrated that the former inhibit cancer progression [4,5]
Other researchers found that normal fibroblasts could induce tumor growth [6,7,8]; further, quiescent fibroblasts can become activated and might be key regulators of paracrine signaling during cancer progression [9]
Summary
Cancer progression has an affinity relationship with the tumor microenvironment, including the extracellular matrix (ECM), fibroblasts, immune cells, and endothelial cells, and the blood vessels and proteins produced [1,2]. Cellular responses can be observed immediately without physical damage and distinguished after fluorescent labeling With this device, we are able to investigate interactions between tumor cells and normal fibroblasts and analyze the function of antitumor drugs with different concentrations in tumor-induced fibroblasts. We are able to investigate interactions between tumor cells and normal fibroblasts and analyze the function of antitumor drugs with different concentrations in tumor-induced fibroblasts This rarely reported co-culture mode provides a cost-effective approach to accomplish multiple functions, including cell loading with passive pumping, heterogeneous cell compartmentalization, and an accurate and reliable cellular assay directly monitored in real time. Multiple types of cells can be contactlessly co-cultured by designing several entrance channels, which enables us to mimic complicated microenvironments in vivo It provides a compartmentalized co-culture model to elucidate reciprocal interactions between heterogeneous cell types within tumors, posing a relevant impact on antitumor therapeutic strategies
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