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Author Notes:

Susan N. Thomas, Ph.D., Georgia Institute of Technology, 315 Ferst Drive NW, IBB Building, Room 2310, Atlanta, GA 30332, Phone: 404.385.1126, Fax: 404.385.1397

Subjects:

Research Funding:

This work was supported by National Institutes of Health R21 CA202849 and NIH T32 GM-008433.

Keywords:

  • Science & Technology
  • Technology
  • Materials Science, Biomaterials
  • Materials Science
  • colon cancer
  • E-selectin
  • metastasis
  • microfluidic
  • sialyl Lewis x
  • VARIANT ISOFORMS
  • P-SELECTIN
  • ROLLING ADHESION
  • TUMOR-METASTASIS
  • LIGANDS
  • CD44
  • TRANSDUCTION
  • PERSISTENCE
  • EXPRESSION
  • MARKERS

Analyzing Mechanisms of Metastatic Cancer Cell Adhesive Phenotype Leveraging Preparative Adhesion Chromatography Microfluidic

Tools:

Journal Title:

ADVANCED BIOSYSTEMS

Volume:

Volume 3, Number 3

Publisher:

, Pages e1800328-e1800328

Type of Work:

Article | Post-print: After Peer Review

Abstract:

An integrated, parallel-plate microfluidic device is engineered to interrogate and fractionate cells based on their adhesivity to a substrate surface functionalized with adhesive ligand in a tightly controlled flow environment to elucidate associated cell-intrinsic pathways. Wall shear stress levels and endothelial presentation of E-selectin are modeled after the inflamed vasculature microenvironment in order to simulate in vitro conditions under which in vivo hematogenous metastasis occurs. Based on elution time from the flow channel, the collection of separate fractions of cells—noninteracting and interacting—at high yields and viabilities enables multiple postperfusion analyses, including flow cytometry, in vivo metastasis modeling, and transcriptomic analysis. This platform enables the interrogation of flow-regulated cell molecular profiles, such as (co)expression levels of natively expressed selectin ligands sLex, CD44, and carcinoembryonic antigen, and cancer stem cell marker CD24. This additionally reveals E-selectin adhesivity exhibited by metastatic human colon carcinoma cells to be a transient phenotype. Facile and rapid, this methodology for unbiased, label free sorting of large populations of cells based on their adhesion in flow represents a method of studying flow-regulated adhesion in vitro for the identification of molecular drug targets for development as antimetastatic cancer therapeutics.
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