The way it moves
The average patient survival rate for glioblastoma, an aggressive type of brain cancer, is about 15 months. Because many affected cells can evade surgery and become resistant to radiation and chemotherapy, learning how and why these cells are so invasive is an important step toward understanding how to stop the invasion itself — and ultimately to finding a cure. Now, new research led by Sanjay Kumar, professor of bioengineering and of chemical and biomolecular engineering, has shed light on how tumor cells adhere to and move through brain tissue.
Every tissue in our bodies consists of cells and material that surrounds those cells; this “extracellular matrix” keeps our tissue from falling apart. In our brains, that relevant material is hyaluronic acid (HA). Previous studies used a synthetic polymer material to mimic brain tissue, but Kumar’s team replaced the polymer with the brain’s own HA. Upon doing so, the team observed that a specialized HA-binding cell surface receptor called CD44 allows tumor cells to form very long microtentacles, establishing a foothold that the cells can use to pull themselves forward and shimmy through the tissue — much like a rock climber grabs ahold of a crevice to advance on the rock face.
Graduate student and study lead author Kayla Wolf recognized that such structures had been seen before, just in a different context. Circulating tumor cells, which have detached from a primary tumor and entered the bloodstream, use microtentacles to attach to blood vessel walls and metastasize. Additionally, the research team identified several proteins involved in the process, some of which turned out to be enriched in highly aggressive tumors and could be further explored as disease biomarkers or drug targets.