Cell Adhesion Strength Used as Marker for Metastatic Potential

A new device that measures the stickiness of cancer cells has been developed by University of California San Diego researchers. The device is being used to measure adhesion strength, which the team believes could serve as a physical marker that identifies highly metastatic cells within a heterogeneous tumor cell population.

This work, published recently in Cancer Research, addresses a longstanding problem in the field of cancer research: it has been difficult to find biological markers to universally identify and select the most aggressive cells in tumors.  "This new device could be the first step to better assess how likely tumor recurrence is," said Adam Engler, senior author of the study. "Patients with few of these aggressive cells lying dormant in their surrounding tissue may be less likely to see a tumor reoccur 5, 10, or 20 years later." Engler noted that by knowing a patient's risk, follow-up treatments could be better tailored to the individual.

The device that Engler's team built consists of a microfluidic chamber coated with an adhesive protein. Cancer cells are placed in the chamber and after they adhere, a fluid is pushed through to detach cells. The faster the fluid moves, the higher the shear stress that the cells experience. The team can isolate cells that detach at specific shear stresses and analyze them. Cells collected at lower shear stress are weakly adherent, while those collected at higher shear stresses are strongly adherent.

Their analysis led the team to another critical finding: weakly adherent cells have a unique genetic signature that identifies them and enables them to migrate and invade faster. Comparing this signature to thousands of patients in the Cancer Genome Atlas database, researchers found that patients with tumors high in this "weakly adherent signature" experienced tumor recurrence occurred earlier and more frequently.

Building on these findings, Engler and his team hope to "prime" tumors with weakly adherent cells to see if they indeed metastasize faster and more frequently. "If our mouse model shows that these cells indeed reduce cancer-free survival times, it will pave the way for substantial prognostic studies in humans with these types of solid tumors," said first author Pranjali Beri.