A Novel, Rapid Approach to Mechanically Predict Metastatic Potential of Cancer Cells

Metastases are the main cause of cancer-related mortality. Invasion of cancer cells through tissue is a critical step in formation of metastases. During invasion, cancer cells change morphology and apply forces to their surroundings. We have previously shown that single, metastatic breast cancer cells from cell-lines apply mechanical forces to indent a synthetic, impenetrable, physiological-stiffness gel, whereas benign breast cells did not; the impenetrable gels effectively isolate mechanical interactions. As metastases from solid tumors occur predominantly by collective invasion, here we focus on the mechanical interactions of cell-clusters with the gel. We show that 56% and 33%, respectively, of high metastatic potential (MP) and low MP cell clusters indent the gel, double the amounts of single cells that had indented; benign cells still do not indent. The indentation depth of high (12±0.2 µm) and low MP cells (9.1±0.3 µm) are significantly different, and are again larger than observed in single cells. Thus, we observe that cells in clusters are more invasively potent. Further, the cell-gel mechanical interactions provide an approach to rapidly distinguish between high and low MP cells.