Speaker
Description
The tumor microenvironment (TME) consisting of blood and lymphatic vessels, fibroblasts, immune cells, and extracellular matrix (ECM) is a critical factor determining prognosis of anti-cancer drug treatment. Most of all, vasculature and ECM structures are the most influential factors in TME. The abnormal, tortuous and leaky tumor vasculature structure reduces chemical drug delivery to target tumor. Moreover, the high-density collagen fibers surrounding the tumor tissues make chemical drugs less effective and inhibit the infiltration of immune cells into the tumor. Therefore, mimicking the vasculature and ECM structures surrounding tumor in vitro is crucial to predict anti-cancer drug efficacy.
Therefore, a detailed and systematic understanding of the vasculature and ECM in the tumor microenvironment is essential for establishing tumor treatment strategies. Although in vivo studies are valuable in deepening our understanding of the interactions between cancer cells and the tumor microenvironment, they have limitations in dissecting the detailed mechanisms of cell-cell interactions. Additionally, results from animal models are difficult to apply to humans due to species differences. Tumor-on-a-chip offers an alternative method to study multicellular interactions in the tumor microenvironment in vitro. Previous studies on tumor-on-a-chip have been developed to incorporate endothelial cells into tumor spheroids to mimic the tumor microenvironmental vasculature and to induce tumor-associated angiogenesis or to create vascular networks with cancer cells. However, they did not consider ECM remodeling even though it is one of the most important factors in the tumor microenvironment.
In this study, we construct a breast cancer microenvironment on a microfluidic 3D cell culture platform using cancer spheroids, fibroblasts, and endothelial cells. To investigate correlating effect of tumor aggressiveness, TME formation and anti-cancer drug efficacy, three different breast cell lines were selected according to surface receptor expression. Their vasculature and ECM structures were compared with each other and the anti-cancer efficacy of paclitaxel (PTX) and NK cell infusion was evaluated using our microfluidic platform. In addition, effect of TME targeting drugs on vasculature and ECM was investigated. The results show more aggressive tumor constructs more inhibitive TME in anti-cancer treatment and that can be recovered by vasculature and ECM targeting drug treatment.
