Microfluidic Device Assesses Stickiness of Tumor Cells to Predict Cancer Spread

Ductal carcinoma in situ (DCIS), a type of early-stage breast cancer, is often referred to as stage zero breast cancer. In many cases, it remains harmless and does not spread beyond the milk ducts where it originates. However, in some instances, DCIS progresses into invasive breast cancer, which can become life-threatening. Despite years of research, determining which cases require aggressive treatment and which can be safely monitored has remained difficult. Clinical decisions about treatment usually depend on the size and grade of the DCIS lesion, but these factors do not always reliably predict the behavior of the cancer. Identifying a better way to predict which cases are likely to become more aggressive could significantly enhance treatment strategies. Now, researchers have discovered a potential method for predicting the likelihood of cancer spreading by assessing the "stickiness" of tumor cells. This breakthrough, made possible by a specially designed microfluidic device, could help doctors identify high-risk patients and tailor their treatment plans more effectively.

The innovative device, developed by scientists at the University of California San Diego (La Jolla, CA, USA), works by pushing tumor cells through fluid-filled chambers and sorting them based on how well they adhere to the walls of the chambers. In tests with tumor cells collected from patients with various stages of breast cancer, the researchers identified a distinct pattern: cells from patients with more aggressive cancers were less sticky (weakly adherent), while cells from patients with less aggressive cancers were more sticky (strongly adherent). The team’s previous research had already shown that cancer cells with weak adhesion are more likely to migrate and invade surrounding tissues, compared to cells with stronger adhesion. By testing this concept on patient tumor samples, the team advanced their work, demonstrating that the adhesion strength of tumor cells varies and that this characteristic might help predict whether a patient’s cancer will spread.

Image: As tumor cells flow through these microfluidic chambers, they are subjected to increasing shear stress and sorted based on their adhesion strength (Photo courtesy of UC San Diego)

The device, about the size of an index card, consists of microfluidic chambers that are coated with adhesive proteins found in breast tissue, like fibronectin. When tumor cells are introduced into the chambers, they adhere to the fibronectin coating. The cells are then subjected to increasing shear stress as fluid flows through the chambers. By observing where cells detach under specific stress levels, the researchers categorize them as weakly or strongly adherent. In their most recent study, the team used this device to examine cell adhesion in DCIS samples. The device was tested in an investigator-initiated trial with samples from 16 patients, including normal breast tissue, DCIS tumors, and aggressive breast cancer tumors from patients with invasive ductal and lobular carcinomas. The results, published in Cell Reports, revealed that aggressive breast cancer samples contained weakly adherent cells, while normal breast tissue samples contained strongly adherent cells. DCIS samples showed intermediate levels of adhesion, but there was significant variability across patients. Moving forward, the team plans to monitor DCIS patients over the next five years to assess whether adhesion strength correlates with metastatic progression. If their hypothesis proves correct, this device could provide oncologists with a powerful tool to inform treatment decisions, potentially recommending more aggressive treatments for patients with tumors showing weak cell adhesion.

“Right now, we don’t have a reliable way to identify which DCIS patients are at risk of developing more aggressive breast cancer. Our device could change that,” said study senior author Adam Engler, a professor in the Shu Chien-Gene Lay Department of Bioengineering at the UC San Diego Jacobs School of Engineering. “Our hope is that this device will allow us to prospectively identify those at highest risk, so that we can intervene before metastasis occurs.”