Analytical cell adhesion chromatography reveals impaired persistence of metastatic cell rolling adhesion to P-selectin.
Selectins facilitate the recruitment of circulating cells from the bloodstream by mediating rolling adhesion, which initiates the cell-cell signaling that directs extravasation into surrounding tissues. To measure the relative efficiency of cell adhesion in shear flow for in vitro drug screening, we designed and implemented a microfluidic-based analytical cell adhesion chromatography system. The juxtaposition of instantaneous rolling velocities with elution times revealed that human metastatic cancer cells, but not human leukocytes, had a reduced capacity to sustain rolling adhesion with P-selectin. We define a new parameter, termed adhesion persistence, which is conceptually similar to migration persistence in the context of chemotaxis, but instead describes the capacity of cells to resist the influence of shear flow and sustain rolling interactions with an adhesive substrate that might modulate the probability of extravasation. Among cell types assayed, adhesion persistence to P-selectin was specifically reduced in metastatic but not leukocyte-like cells in response to a low dose of heparin. In conclusion, we demonstrate this as an effective methodology to identify selectin adhesion antagonist doses that modulate homing cell adhesion and engraftment in a cell-subtype-selective manner.
George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA 30332, USA Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA 30332, USA.
Jaeho
J
Oh
Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA 30332, USA Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA.
Erin E
EE
Edwards
George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA 30332, USA Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA 30332, USA.
P Mason
PM
McClatchey
George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA 30332, USA Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, 315 Ferst Drive NW, Atlanta, GA 30332, USA Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA 30332, USA Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30307, USA susan.thomas@gatech.edu.
Susan N
SN
Thomas
D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002633:Chemotaxis; D002845:Chromatography; D006801:Humans; D009362:Neoplasm Metastasis; D019007:P-Selectin / Q000378:metabolism*
D019007:P-Selectin
Cell adhesion; Metastasis; P-selectin