Fluorometric Quantification of Single Cell Velocities to Investigate Cancer Metastasis

• Authors: Erin Elizabeth Edwards, Emory University; Katherine Gayle Birmingham, Georgia Institute of Technology; Meghan Janne O'Melia, Emory University; Jaeho Oh, Georgia Institute of Technology; Susan Napier Thomas, Emory University
• Journal Title: Cell Systems
• Volume: Volume 7, Number 5
• Publisher: Elsevier (Cell Press) | 2018-11-28, Pages 496-509.e6
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.cels.2018.10.005
• Subjects: Engineering, Biomedical; Health Sciences, Oncology
• Keywords: Cancer Metastasis; Single Cell Velocities

Abstract

Hematogenous metastasis is a multistep, selectin-regulated process whose mechanisms remain poorly understood. To investigate this biological pathway of cancer dissemination and better understand circulating cancer cells, we developed a high-throughput methodology that integrates organ-on-chip-like microfluidic and photoconvertible protein technologies. Our approach can ascribe single cell velocity as a traceable cell property for off-chip analysis of the direct relationships between cell-molecular profiles and adhesive phenotypes in the context of physiologically relevant fluid flow. We interrogated how natively expressed selectin ligands relate to colon cancer cell rolling frequencies and velocities, and provide context for previously reported disparities in in vitro and in vivo models of selectin-mediated adhesion and metastasis. This integrated methodology represents a versatile approach for the development of antimetastatic therapeutics as well as to generate and test mechanistic hypotheses regarding spatiotemporal processes that occur over timescales of seconds to hours with single-cell resolution.