Abstract LB-316: Dynamic live cell imaging of tumor migration and invasion

Abstract

Abstract Migration and invasion activities of metastasizing cancer cells are of immense significance to the field of cancer research, often leading to fatal spread of the disease. While much understanding has been gained regarding the underlying molecular and cellular mechanisms governing these processes, the direct observations of associate morphological and biochemical features are limited by the current methodologies which largely rely on endpoint micro-porous membrane-based assays or various live cell imaging assays performed on 2D/3D substrates- neither of which enable dynamic control over the tumor microenvironment. Microfluidic technologies enable high-resolution time-lapse imaging while providing exceptional experimental control to maintain a physiologically relevant microenvironment. Here we demonstrate the value of the CellASIC ONIX2 “dynamic live cell imaging system”, where microenvironmental parameters such as flowrates, the perfusion of nutrients and reagents, and temperature and gas compositions can be precisely controlled on demand by software during the entire duration of a given experiment. We now show the value of this system for imaging of metastatic processes with a novel microfluidic design comprising two parallel chambers separated by a micro-porous wall. One chamber contains MDA-MB-231 breast cancer cells embedded in 3D hydrogel culture or simply grown in 2D fashion, and the other chamber contains HUVEC endothelial cells in a monolayer. The device enables exceptionally clear real-time imaging of the migration of MDA-MB-231 cells, as well as invasion of these cells through and out of the gel into the “vascular” channel, enabling the monitoring of the adhesion and interaction of these cells with the HUVEC cells once the tumor cells had left the gel. Unlike the state-of-the-art endpoint or static culture imaging assays, the microfluidics system described herein enables the investigation of wider microenvironmental parameters and their interplay with cellular processes in unprecedented precision and permutations, and is also suitable for the studies of wider biological applications outside of cancer biology. Citation Format: Ross Booth, Cindy Chen, Victor Yeh, Deepika Verma, Jun Park. Dynamic live cell imaging of tumor migration and invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-316.