Real-time cancer monitoring via leukocyte adhesion in a biomimetic microfluidic assay

Abstract

Cancer progression involves cell adhesion molecules (CAMs), which facilitate the recruitment of leukocytes and metastatic tumor cells to distant organs by mediating adhesion with endothelial cells. While CAM-mediated tumor dissemination is well studied, the diagnostic potential of CAM ligand-expressing activated leukocytes as biomarkers reflecting the host's inflammatory response to cancer remains relatively unexplored. This study presents a microfluidic device that assesses cancer-driven leukocyte activation in a 4T1 breast cancer mouse model by quantifying leukocyte adhesion to CAM-coated microchannels under physiological flow conditions. In a 4T1 mouse model, inflammation induces upregulation of CAM ligands that enhance selectin-mediated adhesion between leukocytes and endothelial cells. The proportion of leukocytes expressing CAM ligands correlates with cancer progression, accompanied by an approximately 40-fold enhancement in leukocyte adhesion within a vascular endothelium-mimicking microchannel coated with CAMs following implantation of 4T1 cells in mice. Quantification of leukocyte adhesion in this system discriminates experimental conditions corresponding to primary tumor growth, chemotherapeutic response, and postsurgical recurrence or metastasis in the 4T1 mouse model. These findings establish leukocyte adhesion profiling in a biomimetic microfluidic assay as a functional biomarker of cancer-driven inflammation in vivo and support its potential as a complementary tool for translational cancer monitoring.