In Situ Analysis of Interactions between Fibroblast and Tumor Cells for Drug Assays with Microfluidic Non-Contact Co-Culture

Micromachines (Basel). 2018 Dec 17;9(12):665. doi: 10.3390/mi9120665.

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.

Keywords: co-culture; laminar flows; paracrine signaling.