ICAM-1 expression determines malignant potential of cancer

Solid tumor cells bind to ICAM-1 on endothelial surfaces via MUC-1. Tumor binding to ICAM-1 auto-upregulates tumor ICAM-1 at the leading edge of the tumor and promotes release of chemoattractants for circulating macrophages, and circulating macrophages bind to tumor-expressed ICAM-1, invoking propagation of further chemokines and cytokines that recruit neutrophils. Tight adherence between cell surface ligands on neutrophils and tumor-expressed ICAM-1 activates neutrophils to degranulate, releasing elastases, which break down endovascular and endolymphatic barriers permitting transendothelial tumor cell migration. Consequently, tumor cell ICAM-1 expression dictates metastatic potential and metastatic potential determines cancer lethality.