Cells’ remodeling abilities may be key to how cancer spreads

Research at Oregon State University released Monday shows that human cells have tremendous power to mechanically change their surroundings, opening the door to new insights on a variety of physiological processes — including how cancer spreads.

These irreversible mechanical remodels are different from the chemical changes to the extracellular matrix that cells also induce, and happen much faster – taking place in a few minutes and triggering the chemical remodels, which occur over hours and days.

“Collagen is a major component of our connective tissues,” said OSU biophysicist Bo Sun, co-corresponding author on the study. “Our tissue is constantly changing, and biochemical interactions between cells and the collagen matrix are crucial for maintaining the integrity of living tissue. But cells also interact with the matrix physically – there are pushing forces from membrane protrusions and pulling forces from cell contraction.”

The mechanical changes resulting from those forces had been widely assumed to be reversible – that once the force was released, the matrix would bounce back into its former configuration.

“Those assumptions of small and reversible deformations are now questionable,” Sun said. “Collective contraction between cell clusters may cause large, permanent deformations in the extracellular matrix. We found that a single pair of breast cancer cells can increase the local fiber density of reconstituted collagen matrices by more than 150 percent.”

Sun and collaborators from the OSU College of Science, Rice University and the University of Michigan call the remodeled matrix microstructure between two cells the “collagen bundle.”

“The collagen matrix’s plasticity suggests a new way for cells to interact in tissues,” Sun said. “The collagen bundle from a pair of cells gives microstructural guidance to nearby cells through contact guidance and also creates micromechanical guidance to nearby cells through durotaxis.”

Durotaxis refers to migration in which cells, guided by the structural properties of the extracellular matrix, head toward tissue areas of greater stiffness and density.

“Usually, a solid tumor is associated with a rigid, densified collagen matrix around it,” Sun said. “One good example is breast cancer, where you can feel a lump because the cancer has solidified a large region around it. This research helps further our basic understanding of the whole process.”

The mechanical remodeling – which occurs without the creation or degradation of any fibers – affects an array of physiological processes from cancer metastasis to wound healing to embryo development, Sun said.

“The mechanical remodeling is an early event that triggers a cascade of amplifying events that lead to the chemical remodeling,” he said. “There are two very simple mechanisms for the plasticity to happen: Fibers and polymers disassociate and reform, or fibers and polymers bundle. In such ways our tissue tries to relax the cancer cell-generated stress, and goes through unrecoverable aging.”

The National Science Foundation supported this research. Findings were published in Nature Communications.