Abstract 1547: Characterization of receptor-ligand interactions between head and neck circulating tumor cells and E-selectin

• Published in: Cancer research (Chicago, Ill.) Vol. 71; no. 8_Supplement; p. 1547
• Main Authors: Marshall, Jocelyn R., Reynolds, Nathan M., Abram, Courtney E., Henson, Karissa A., Wood, S. Matthew, Nimrichter, Leonardo, Burdick, Monica M.
• Format: Journal Article
• Language: English
• Published: 15.04.2011
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2011-1547

Abstract Though the exact mechanisms of cancer metastasis are not known, it is widely believed that circulating tumor cells (CTCs) that have broken off from the primary tumor flow through the blood stream until ligands on their surface recognize receptors present on the vascular endothelium. From there, CTCs loosely attach to the endothelium surface and roll until they become firmly adherent. Cells then migrate through the blood vessel walls to establish metastatic colonies in a distant organ. Therefore, identifying the molecular structures available for adhesion on the surface of the CTCs is compulsory to fully understanding the ubiquitous and unique natures of cancer metastasis. We have previously shown that the adhesion of head and neck squamous cell carcinomas (HNSCCs) to human umbilical vascular endothelium cells (HUVECs) under flow is mediated by E-selectin present on the endothelium surface. In this study, we investigated the interaction of E-selectin with ligands present on the HNSCC surface. Protease-treated cells of the JHU-011-SCC, JHU-013-SCC, and FaDu cell lines perfused through the parallel-plate flow chamber tethered to and rolled on the HUVECs at a greater incidence rate compared to untreated control cells. These binding interactions were sialidase and fucosidase sensitive. Altogether, these results indicate that sialofucosylated glycolipids on HNSCC cells predominantly contribute to the adhesion of these cells to endothelium. This observation was further confirmed by probing western blots of SDS-PAGE resolved HNSCC lysates with HECA-452 mAb and E-selectin chimera. Neither probe was reactive with protein species. We also tested if a shielding effect of hyaluronic acid (HA) prevented glycosphingolipid engagement to E-selectin. When HNSCC cells were treated with HAse and when hyaluronic acid synthase-3 was silenced by shRNA, there was an increase in cell adhesion events. These results clearly demonstrate that proteins and HA exert shielding effects on the E-selectin glycolipid ligands, thus affecting the overall metastatic ability of the HNSCCs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1547. doi:10.1158/1538-7445.AM2011-1547