Abstract A15: Development of an in vitro 3D vessel-spheroid model for investigating cancer metastasis

Abstract

During metastasis, cells break free from the primary tumor, migrate through the stroma and enter either the vascular or lymph systems to disseminate into secondary sites. To better understand this process, many groups have developed in vitro models of cancer metastasis using microfluidic based platforms to mimic the tumor microenvironment and the intravasation/extravasation of tumor cells. While these models have provided significant new insights into the mechanisms by which metastatic cells move across the endothelium, they are most often focused on the movement of single cells. Notably, there is significant clinical evidence to suggest that tumor cells can travel collectively though the stroma and can circulate as cell aggregates in the vasculature. Recent advances in the understanding of cancer metastasis have shown that cancer may move more aggressively as a collection of cell when traversing the extracellular matrix (ECM) of the tumor microenvironment as opposed to more studied singular cellular motif. To better mimic these collective movements, we have developed a model that incorporates the following essential elements that exist in the tumor microenvironment: a cylindrical channel lined with a confluent monolayer of endothelial cells, a metastatic tumor analog in close proximity to the channel, the ability to incorporate flow with tunable properties to simulate shear stress due to blood flow, and a tunable collagen microenvironment. Briefly, in a 3D printed cube, Type 1 collagen is added at physiological stiffness. As the collagen is polymerizing in the device, a metastatic tumor analog (spheroid) consisting of labeled MDA-MB-231 cells is placed in proximity of the vessel that is lined with endothelial cells. The platform allows for the visualization of metastatic cell intravasation using confocal microscopy. Notably, this model is easy to build and implement with fairly accessible tools and without the use of a clean room or microfabrication facilities. Importantly, going forward this model has the ability to study the cellular behavior post-intravasation due to the incorporation of physiological flows within the channel. Citation Format: Adam Munoz, Joseph Miller, Cynthia A. Reinhart-King. Development of an in vitro 3D vessel-spheroid model for investigating cancer metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr A15.