How Cancer Cells Change Shape and Migration Strategies to Invade Tissue

Oregon State University research has shed new light on the way malignant cells change their shape and migration techniques to invade different types of tissue. The findings were published in Scientific Reports.  

How well a cancer cell can change shape and shift travel modes plays a huge role in a cancer patient’s prognosis, study leader Bo Sun explains. “Many cancer therapies that target a particular way a cell moves can fail to stop tumor metastasis in large part because cells switch to another available migration program,” he said.

Sun and collaborators in the OSU colleges of Science and Engineering used computer vision to track a cell’s migration program based on its shape. For this study, the scientists looked at cells from MDA-MB-23, a line of highly invasive breast cancer cells.  “Cell shape is determined by cell function, and loss of characteristic shape is associated with functional abnormality,” Sun said. “That’s why shape characterization has been an important tool for diagnosis in cancer as well as in other conditions such as red blood cell disease or neurological disorders.”

The machine learning and visualization techniques the scientists employed showed that a cell’s shape changes are regulated by the molecular control hub, Rho/ROCK-signaling, that a cell uses to sense its physical environment and generate the force required for motion. Using a model representing two mechanically distinct layers of extracellular matrix, the scientists showed the cells gradually changed their shape and movement program as they approached and crossed the interface of the layers. That suggests these transitions are essential for cancer cell metastasis, which requires the navigation of non-uniform ECM.

“The way a cell’s form changes—its morphodynamics—is a crucial factor in determining its invasive potential and to our knowledge, this has largely gone unstudied,” Sun said. “The morphodynamics of migrating cancer cells are shaping up to be a powerful tool for inspecting the internal state and microenvironment of the cells. Future research is needed to decode the morphodynamics into a rich and understandable body language of cells, and to affect morphodynamics as a means of controlling what the cells are doing.”