E-selectin-mediated rolling facilitates pancreatic cancer cell adhesion to hyaluronic acid

Daniel J. Shea, Yi W. Li, Kathleen J. Stebe, Konstantinos Konstantopoulos

Research output: Contribution to journalArticlepeer-review

Abstract

Tumor cell extravasation is a multistep process preceded by cell rolling and arrest on the vessel wall via the formation of specific receptor-ligand bonds. The strength, availability, and number of receptor-ligand bonds regulate the rate by which tumor cells tether, roll, and adhereto vascular walls. Although the mechanics ofselectin-mediated rolling have been extensively studied, little is known regarding how tumor cell rolling on selectins facilitates adhesion to a distinct substrate-bound protein with different kinetic properties. By using multicomponent protein patterning and a microfluidic system, we evaluated how E-selectin-dependent rolling modulates hyaluronic acid (HA) adhesion as a function of fluid shear, contact time, and the spacing between E-selectin and HA regions patterned on the substrate. We show that tumor cells rolling on E-selectin were ∼40-fold more likely to bind to HA than nonrolling cells in shear flow. Furthermore, E-selectin-dependent rolling promotes adhesion to HA by both physically slowing cells and enabling them to position proximal to the surface, thereby increasing the on rate of adhesion. A better understanding of tumor cell adhesion under physiologic shear would lead to the development of new diagnostic assays and pave the way to clinical approaches aimed ultimately to halt metastasis.

Original languageEnglish (US)
Pages (from-to)5078-5086
Number of pages9
JournalFASEB Journal
Volume31
Issue number11
DOIs
StatePublished - Nov 2017

Keywords

  • CD44v
  • Cell rolling
  • PODXL

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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