Colon carcinoma cell glycolipids, integrins, and other glycoproteins mediate adhesion to HUVECs under flow.
This study was undertaken to investigate the molecular constituents mediating LS174T colon adenocarcinoma cell adhesion to 4-h TNF-alpha-stimulated human umbilical vein endothelial cells (HUVECs) under flow. At 1 dyn/cm(2), approximately 57% of cells rolled and then became firmly adherent, whereas others continuously rolled on endothelium. Initial cell binding was primarily mediated by endothelial E-selectin. By using neuraminidase, glycolipid biosynthesis inhibitor d,l-threo-1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol. HCl, trypsin, and flow cytometry, LS174T cells were shown to express sialyl Lewis(x) (sLe(x))- and di-sLe(x)-decorated, but not sLe(a)-decorated, glycolipid and glycoprotein ligands for E-selectin. The cells preferentially employed sialylated glycoproteins over glycolipids in adhesion as measured by conversion of rolling to firm adhesion, resistance to detachment by increased shear stress, and rolling velocity. However, a nonsialylated E-selectin counterreceptor also exists. Furthermore, LS174T alpha(2), alpha(6), and beta(1) integrins support a minor pathway in adhesion to HUVECs. Finally, tumor cell attachment specifically increases HUVEC endocytosis of E-selectin. Altogether, the data indicate the complexity of carcinoma cell-endothelium adhesion via sialylated glycoconjugates, integrins, and their respective counterreceptors.
Burdick
Monica M
MM
Department of Chemical Engineering, The Johns Hopkins University, Baltimore, Maryland 21218-2694, USA.
McCaffery
J Michael
JM
Kim
Young S
YS
Bochner
Bruce S
BS
Konstantopoulos
Konstantinos
K
D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006017:Glycolipids / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D012039:Regional Blood Flow / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D019040:E-Selectin; D006017:Glycolipids; D006023:Glycoproteins; D016023:Integrins; D014409:Tumor Necrosis Factor-alpha