title: Profiling Functional and Biochemical Phenotypes of Circulating Tumor Cells Using a Two-Dimensional Sorting Device.
abstract: During cancer progression, tumors shed circulating tumor cells (CTCs) into the bloodstream. CTCs that originate from the same primary tumor can have heterogeneous phenotypes and, while some CTCs possess benign properties, others have high metastatic potential. Deconstructing the heterogeneity of CTCs is challenging and new methods are needed that can sort small numbers of cancer cells according to their phenotypic properties. Here we describe a new microfluidic approach that profiles, along two independent phenotypic axes, the behavior of heterogeneous cell subpopulations. Cancer cells are first profiled according to expression of a surface marker using a nanoparticle-enabled approach. Along the second dimension, these subsets are further separated into subpopulations corresponding to migration profiles generated in response to a chemotactic agent. We deploy this new technique and find a strong correlation between the surface expression and migration potential of CTCs present in blood from mice with xenografted tumors. This system provides an important new means to characterize functional diversity in circulating tumor cells.
authors.affiliation: Department of Electrical and Computer Engineering, University of Toronto, Toronto, ON, Canada.
authors.forename: Mahla
authors.initials: M
authors.lastname: Poudineh
authors.affiliation: Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Labib
authors.affiliation: Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
authors.forename: Sharif
authors.initials: S
authors.lastname: Ahmed
authors.affiliation: Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
authors.forename: L N Matthew
authors.initials: LN
authors.lastname: Nguyen
authors.affiliation: Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
authors.forename: Leyla
authors.initials: L
authors.lastname: Kermanshah
authors.affiliation: Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.
authors.forename: Reza M
authors.initials: RM
authors.lastname: Mohamadi
authors.affiliation: Department of Electrical and Computer Engineering, University of Toronto, Toronto, ON, Canada.
authors.forename: Edward H
authors.initials: EH
authors.lastname: Sargent
authors.affiliation: Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.|Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada.|Department of Biochemistry, University of Toronto, Toronto, ON, Canada.
authors.forename: Shana O
authors.identifier: 0000-0003-3360-5359
authors.initials: SO
authors.lastname: Kelley
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D002469:Cell Separation / Q000295:instrumentation; D002633:Chemotaxis; D004867:Equipment Design; D005260:Female; D006801:Humans; D056656:Lab-On-A-Chip Devices; D008297:Male; D016513:Mice, SCID; D009369:Neoplasms / Q000473:pathology*; D009360:Neoplastic Cells, Circulating / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000473:pathology
keywords: aptamers; cancer; chemotaxis; microfluidic devices; surface marker expression