According to the American Cancer Society, more than 90% of cancer-related suffering and deaths are associated with metastasis. While scientists now understand quite a bit about how cancer cells grow, less is known about how they spread through the body, compromising vital organs as they go.
“We think a huge contributor to this dispersion of cancer cells throughout the body is physics,” said Denis Wirtz, a researcher at the Johns Hopkins University School of Medicine. “And what I mean by physics is not just the physical properties of the cells themselves. We also need to consider the physical properties of the microenvironment those cells travel in.”
The microenvironment near a tumor is collagen-rich, making it denser and stiffer, providing “railways” for the tumor cells to move to other body tissues. Yet, Wirtz argued that the fundamental question of how the cancer cells move through that space was difficult to answer since studies of cell migration were historically confined to the 2D space of the culture dish.
“Based on that 2D microenvironment, people presumed the cells migrated in a random way, that they just simply wandered around like a kind of drunken man until they bumped into something,” Wirtz said. “But cells in the body move in three-dimensional space. And the way cells explore a 3D space might be quite different than the 2D case.”
To test this idea, Wirtz and colleagues stepped away from 2D substrates and followed cell migration in a 3D collagen matrix. “The literature is full of studies that say this is random. But when we looked at the trajectories of the cell, we did not see randomness,” Wirtz said. “As the cells move through the matrix, they digest the matrix; they chew on it and create these channels behind them. But at some point, they stop, turn around and go back, and partially explore the channel they just created. The cells are undergoing trajectories that are more rectilinear than you see in a 2D dish. And, as such, the criteria of randomness is just not met.”
According to Wirtz, better understanding the physics of how cells migrate in 3D space will open a window of opportunity to stop metastatic disease. By using molecules that can regulate cell migration in 3D space, clinicians might be able re-direct cancer cells and stop them from ever invading other tissues.
“Once the cancer cells are in the blood vessels, it’s too late. It is possible that we can find ways to force these cells to move in different ways so they essentially miss those targets,” he said. “We still need to test these ideas in animals, but it could be a beautiful strategy.”
Wu PH, Giri A, Sun SX, Wirtz D. Three-dimensional cell migration does not follow a random walk. Proc Natl Acad Sci U S A. 2014 Mar 4