Microscopy image of a tumor cell migrating through collagen. [Ryan Petrie]
Microscopy image of a tumor cell migrating through collagen. [Ryan Petrie]

Researchers at the Drexel College of Arts and Science, led by assistant professor Ryan Petrie, Ph.D., say they were able to determine that certain tumor cells (fibrosarcoma) are unable to perform a certain kind of movement that normal connective tissue cells perform when moving through tight, three-dimensional environments. Since cells' nuclei are big and rigid, they're not easy to squeeze through three-dimensional structures. When such a structure, or matrix, is encountered, normal cells can switch to a form of movement that creates a pressure differential inside the cell by moving their nucleus, like a piston in an engine.

But Dr. Petrie's research found that fibrosarcoma cells can't perform this piston movement to get through those tight squeezes when certain protease enzymes are present and highly active. Thus, these tumor cells effectively chew their way through the matrix, while normal cells use powerful molecular motors to muscle their way forward and leave the matrix more intact.

Dr. Petrie's team study (“Activating the Nuclear Piston Mechanism of 3D Migration in Tumor Cells”), published in the January 2 issue of the Journal of Cell Biology, studied this movement of cells, and lack thereof, in rat tail and cattle skin collagen.

“Cell migration is a lethal characteristic of metastatic tumors, where malignant cells begin to move inappropriately and spread through the body to form secondary tumors,” said Dr. Petrie. “To fully understand the mechanisms that drive normal and pathological cell movement, we must study cell migration in three-dimensional environments, such as the ones found in our tissues.

“Therapeutically preventing the inappropriate movement of metastatic tumor cells could be used in combination with existing chemotherapies to increase patient survival,” added Dr. Petrie.

The research has implications beyond just fighting cancer cells.

“Promoting movement of fibroblasts in specific three-dimensional tissues like dermis [skin] and cartilage could help to heal difficult-to-treat wounds,” Dr. Petrie explained. “Understanding the fundamental molecular mechanisms driving the movement of these cell types will be essential for designing rational therapeutic strategies in the future.”

Determining the different methods in movement between normal and malignant cells is important, but more research needs to be done to find out exactly why there is a difference.

“The next step will be to untangle the intracellular signaling pathways that dictate cell behavior to understand precisely why tumor and normal cells move differently in the same three-dimensional environment,” noted Dr. Petrie. “We speculate these signaling pathways will provide the best candidates for drugs aimed at promoting or reducing cell movement in the future.”