A New Dimension in Early Cancer Screening: Stronger Cell Adhesion = Lower Risk? UC San Diego Scientists Develop Cell Adhesion-Based Cancer Detection Technology

Recently, researchers at the University of California, San Diego (UC San Diego) have developed a microfluidic-based adhesion test for risk stratification in breast cancer patients. The latest research findings were published in Cell Reports.

Adam Engler, a professor of bioengineering at UC San Diego and one of the developers of the test, stated that based on nearly a decade of research in cell adhesion biology, the research team decided to use this test to verify whether there are differences in adhesion between non-malignant/non-metastatic cell lines and malignant/metastatic cell lines. Engler noted that the team found that non-malignant cells "adhere to their surroundings like glue," exhibiting "very low migratory capacity" and "strong adhesion to the extracellular environment," while metastatic cells do not possess these characteristics. The team first published related results in 2017, and the new paper published recently in Cell Reports is a deepened study based on this earlier work.

In the latest research, the team used a microfluidic device equipped with variable-width chambers (divergent wall parallel plate flow chambers) to analyze resected tumor cells. The device features a wide inlet that gradually narrows to a chamber coated with breast tissue adhesion proteins, where tumor cells are placed for imaging. By pumping liquid to detach the cells from the adhesion proteins, researchers can determine whether the cells are weakly or strongly adhesive.

Through adhesion experiments on mouse and human cells, the team found that in mouse models, weakly adhesive cells have a significantly higher rate of forming secondary metastatic lesions compared to strongly adhesive cells. In addition to animal experiments, the researchers also observed the behavior of cells in 16 human samples, including normal breast tissue, ductal carcinoma in situ (DCIS), and invasive lobular/carcinoma. The data showed that in the mouse experiments, the adhesion test retrospectively predicted metastatic disease with 100% specificity, 85% sensitivity, and an AUC of 0.94. The study revealed a significant correlation between strongly adhesive cells in patients without disease and weakly adhesive cells in patients with invasive disease. The microfluidic device has already been patented, and Engler's team has established a startup company for patent licensing and commercialization.

Regarding human samples, the researchers wrote, "Single-cell populations from healthy breast tissue exhibited the strongest adhesion, DCIS cell populations had intermediate average adhesion strength, and tumor cells from invasive ductal carcinoma (IDC) and lobular carcinoma (ILC) showed the weakest adhesion." Engler stated that this method is particularly suitable for patients with low-grade tumors (cells proliferate but have not yet begun to spread), as these patients have significant differences in prognosis. Existing histological markers are difficult to predict whether DCIS patients will progress to metastatic disease, but this device has the potential to provide clinicians with additional data to support treatment decisions.

In the future, the results of this test could assist in formulating treatment plans: if DCIS patients show weakly adhesive cells, clinicians may need to adopt a more aggressive treatment approach. Currently, the clinical utility of the device still needs to be verified, and large-scale clinical trials are required to determine the threshold values for strong and weak adhesion. It is reported that the startup company plans to conduct clinical trials on hundreds of DCIS patients to precisely define risk stratification standards. The clinical version of the test will output a score between 0 and 1000, with scores close to 1000 indicating strongly adhesive cells and scores close to 0 indicating non-adhesive cells (no migratory capacity). Engler pointed out that there is a "golden zone" that marks the most aggressive tumors, and validation trials will clarify the boundaries of this zone.

"All solid tumors initially present as masses within host tissues, after which cells inevitably spread in some way," Engler explained. "Physical principles apply not only to tumor growth but also to the metastatic process." He noted that metastatic cells must differ in physical properties from those in situ. The research team has verified that invasive lung and prostate cancer cell lines share the same characteristics as breast cancer cell lines. Engler believes that "the key role of cell adhesion in the metastatic process" may apply to all solid tumors. Currently, graduate students in his laboratory are studying pancreatic cancer cells to test the universality of this theory.