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

Abstract

Tumor cell extravasation is a multistep process preceded by cell rolling and arrest on the vessel wall 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 adhere to vascular walls. Although the mechanics of selectin-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.-Shea, D. J., Li, Y. W., Stebe, K. J., Konstantopoulos, K. E-selectin-mediated rolling facilitates pancreatic cancer cell adhesion to hyaluronic acid.

Knockdown of α2,3-Sialyltransferases Impairs Pancreatic Cancer Cell Migration, Invasion and E-selectin-Dependent Adhesion

“…Taken together, these findings reveal that sLe x is critical to the binding of PDA cells to human E-selectin in vitro. To further investigate the functional importance of ST3GAL4 and ST3GAL3 in the binding of pancreatic tumor cells to E-selectin, we also analyzed this adhesive interaction under dynamic flow conditions using a microfluidic system [43]. Using this system, we perfused SC and KD BxPC-3 and Capan-1 cells under a shear stress level of 1.1 dyn/cm 2 over immobilized E-selectin ( Figure 9B).…”

Glycocalyx-Mediated Vascular Dissemination of Circulating Tumor Cells

“…The GCX has 19 traditionally been viewed as a repulsive barrier that prevents adhesion due to the dense, charged, 20 and hydrated nature of its main components, such as hyaluronic acid (HA), heparan sulfate (HS), and 21 chondroitin sulfate (CS) 19,20 . Curiously, the GCX on TCs is particularly over-expressed and robust, yet 22 it seems to enhance adhesion of TCs to both the normal and inflamed endothelium [21][22][23] . As such, the 23 role of the GCX in TC adhesion and trans-endothelial migration is not yet resolved.…”

A nutrigenetic approach for investigating the chemopreventive effects of black raspberries during the development of preneoplastic esophagi in rats

“…NPPB was decreased by tolfenamic acid, which suppressed cell proliferation and increased apoptosis in colon tumors [69]. E-selectin ( SELE ) promoted the matrix adhesion of pancreatic cancer cells [70]. These results suggest that RELT , KRT16 , NPPB , and SELE are involved in the tumorigenesis.…”