Cell-to-cell adhesion via CD54 (intercellular adhesion molecule-1)-associated cell proliferation in diffuse large...

Cluster of Differentiation 54 (CD54), also known as intracellular adhesion molecule-1 (ICAM-1), is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. Although CD54 has been shown to be involved in cell-to-cell adhesion and proliferation of B-cell lymphoma cell lines, the clinical significance of its expression has not yet been elucidated. We analyzed Ki-67 indices, the expression status of CD54 and its receptor (CD11a), and the intercellular distance of tumor cells in 40 diffuse large B-cell lymphoma (DLBCL) cases with vascular invasion to analyze the association of cell adhesion and proliferation status. CD54 and CD11a were simultaneously expressed (double-positive) in extra/intravascular tumor cells in 14 (35%) of the cases. Histologically, lymphoma cells of the double positive cases exhibited significantly higher Ki-67 index in extravascular tumor cells than that in the intravascular ones, while no difference was observed in lymphoma cells of the non-double positive cases. The significantly shorter extravascular intercellular distance compared with the intravascular intercellular distance suggested the association between cell-cell adhesion mediated by CD54 and cell proliferation. We further confirmed that the treatment of the recombinant LFA1 (CD11a/CD18) showed the adhesion of human DLBCL-derived cell line HBL-2 to LFA1 and increased cell viability. These findings suggest that cell-to-cell adhesion via CD54 maintains the cell proliferative activity of a subset of DLBCL. This study provides a valuable foundation upon which further research may be conducted to determine detailed mechanisms of cell-to-cell-associated and adhesion-independent cell proliferation.