Vascular Recruitment of Human Retinoblastoma Cells by Multi-Cellular Adhesive Interactions with Circulating Leukocytes.

Abstract

Retinoblastoma (RB) is a retinal cancer of childhood. RB survivors tend to develop additional tumors later in life, although the physical mechanisms of RB metastatic spread are largely unknown. One step in metastasis through the blood stream is tumor cell adherence to the blood vessel wall through specific receptor:ligand interactions. Yet, human RB cell lines RB143 and WERI-Rb27 do not express selectin ligands or beta-2 integrins and cannot directly interact with inflamed endothelium. In this study, we show that RB cells express ICAM-1, a beta-2 integrin ligand that correlates with metastasis and is preferentially co-expressed on RB cells that also express ABCG2, a stem cell marker associated with chemoresistance and metastasis. Based on the presence of ICAM-1+ RB cells, we tested the hypothesis that RB cells could be recruited to an E-selectin surface via attachment to activated polymorphonuclear cells (PMNs). We characterized the dynamic adhesion between RB cells and PMNs within E-selectin coated microtubes under a physiological range of wall shear stress values (0.2-5 dyn/cm2). We show that activated PMNs are necessary for the recruitment of RB cells through ICAM-1:LFA-1 binding. Results from this work may lead to new strategies that target the metastatic spread of tumor cells.