Biomimetic Cell Adhesion Boosts Cancer Prognosis

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.

A new microfluidic technology that leverages immune cell behavior is set to transform cancer monitoring, thanks to researchers at UNIST.

Led by Professor Joo Hun Kang in the Department of Biomedical Engineering at UNIST, the team has introduced a novel diagnostic chip that analyzes the adhesion properties of leukocytes, or white blood cells, to detect cancer recurrence and evaluate the effectiveness of chemotherapy. Unlike traditional liquid biopsy approaches that directly seek circulating tumor cells, this innovative method taps into the body's immune response-specifically, the increased adhesion capacity of leukocytes induced by tumor-related inflammation.

This cutting-edge device provides a minimally invasive, real-time window into the patient's immune system, enabling early detection of minimal residual disease-a critical factor often missed by imaging techniques such as MRI or CT scans. It also offers a cost-effective complement to existing liquid biopsy technologies, providing dynamic insights into treatment response and disease progression.

The core of this system is a microfluidic chip, composed of ultra-thin microchannels, through which a small volume of blood is passed. The chip is coated with specialized proteins that mimic the natural adhesion molecules involved in immune cell interactions. When blood flows through these channels, leukocytes with activated adhesion receptors-stimulated by inflammation from tumor tissue-attach to the coated surfaces.

An integrated software module automatically counts the number of adhered leukocytes, providing quantitative data on immune activation. This adhesion is amplified by the release of inflammatory molecules from tumor tissue, which activate cell adhesion molecules (CAMs) on leukocytes-molecular structures that mediate cell-cell and cell-extracellular matrix interactions.

In preclinical experiments using a mouse model of breast cancer, leukocytes from tumor-bearing mice exhibited up to 40 times more adhesion in the microchannels compared to healthy controls. This heightened adhesion correlated with tumor activity and inflammation levels.

Moreover, the system demonstrated remarkable sensitivity to changes induced by chemotherapy. For example, administration of doxorubicin-a standard anti-cancer drug-immediately reduced leukocyte adhesion levels, aligning with tumor shrinkage observed through other measures. Conversely, ineffective treatments maintained or increased adhesion levels, indicating ongoing tumor activity.

The device also detected early signs of metastatic spread after primary tumor removal. Leukocyte adhesion levels initially decreased post-surgery but then increased again during early metastatic phases, suggesting potential for early relapse detection before clinical or radiological signs emerge.

Professor Kang explained, "This approach enables clinicians to detect early relapse and monitor treatment efficacy by analyzing the immune response-specifically, leukocyte adhesion-rather than relying solely on imaging or invasive biopsies. It opens the door to more personalized, timely interventions, reducing unnecessary treatments and improving patient outcomes."

The research was participated by Brian Choi from UNIST, as the first author, with support from the National Research Foundation of Korea (NRF), the Ministry of Science and ICT (MSIT), the Ministry of Health & Welfare (MOHW), the Korean Fund for Regenerative Medicine (KFRM), and the Ministry of Trade, Industry & Energy (MOTIE).

This research, led by first authors from UNIST and Brian Choi, was supported by the National Research Foundation of Korea (NRF), the Ministry of Science and ICT (MSIT), the Ministry of Health & Welfare (MOHW), the Korean Fund for Regenerative Medicine (KFRM), and the Ministry of Trade, Industry & Energy (MOTIE). The findings were published on March 1 in *Biosensors and Bioelectronics*, an international journal published by Elsevier.

The study was published in Biosensors and Bioelectronics, an international journal published by Elsevier on March 1, 2026.

Journal Reference

Brian Choi, Seyong Kwon, Min Seok Lee, et al., "Real-time cancer monitoring via leukocyte adhesion in a biomimetic microfluidic assay," Biosens. Bioelectron., (2026).