OP54: HETEROPHILIC INTERACTION OF CD62E AND CD15 MEDIATES ADHESION OF METASTATIC NON-SMALL CELL LUNG CANCER CELLS TO BRAIN ENDOTHELIUM

INTRODUCTION: CD15, a cell adhesion molecule which is overexpressed in various cancers, is thought to be a key player in non-central nervous system (CNS) metastasis. However, the role of CD15 in brain metastasis is largely unexplored. CD15, a trisaccharide adhesion molecule, is over-expressed in non-CNS metastatic cancers. The role of CD15/CD62E interaction in lung to brain metastasis is still unexplored. The aim of this study is to therefore provide a better understanding of CD15/CD62E interaction and its role in adhesion in brain metastasis. METHOD: Expression of CD62E and CD15 were evaluated in brain microvascular endothelial cells (hCMEC/D3), primary (A549 and COR-L105) and metastatic NSCLC cells (NCI-H1299, SEBTA-001 and SEBTA-005) using flow cytometry (FC), immunocytochemistry (ICC) and Western blotting (WB). Adhesion assays under static conditions and physiological flow (shear stress 2.5 dyn/cm2) conditions were conducted. Immunoblocking of CD15 was performed to investigate its role in adhesion. RESULTS: Low levels of CD15 was seen on hCMEC/D3 (19.69%) compared to metastatic NSCLC cells (NCI-H1299: 79%, SEBTA-001: 54% and SEBTA-005: 39%) and primary NSCLC (COR-L105: 31% and A549: 23%) cells (P < 0.001). CD62E expression was high in hCMEC/D3 cells activated with TNF-α. Metastatic NSCLC adhered most strongly to hCMEC/D3 compared to primary NSCLC cells. CD15 immunoblocking blunted this adhesion under static and shear stress conditions (p < 0.001), confirming the correlation between CD15 and cerebral metastasis. CONCLUSION: This study enhances understanding of lung cancer cell-brain endothelial adhesion and suggests that CD15 may play a role in adhesion in concert with TNF-α activation of its binding partner CD62E.