New insights into how tumor cells move could greatly assist in developing treatments to prevent the spread of cancer.
Using an experimental model, scientists from the University of Minnesota in Minneapolis stopped cancer cells from spreading, even after the cells had altered their mode of movement.
The chances of eliminating cancer are much higher if the disease has not spread beyond the primary tumor.
Around 90 percent of cancer-related deaths occur because of metastasis, or the ability of tumors to invade nearby tissue and spread to other parts of the body.
A treatment that stopped the movement of cancer cells would greatly improve survival rates, by giving doctors more time to deal with the primary tumor.
The new study, featured in the journal Nature Communications, could mark a big step toward this achievement.
'Cancer cells are very sneaky'
The researchers set up laboratory versions of a tumor environment and observed how breast cancer cells moved through them.
Using drugs, they tried to stop the cells by disrupting the mechanisms that serve as motors, generating the forces for movement.
To the scientists' surprise, the cells switched to a completely different way of moving, causing them to resemble "oozing" blobs.
"Cancer cells are very sneaky," remarks senior author Dr. Paolo P. Provenzano, an associate professor in the University of Minnesota's biomedical engineering department. He admits, "We didn't expect the cells to change their movement."
By targeting both modes of cell movement at the same time, however, the researchers "stopped the cells in their tracks."
Dr. Provenzano notes, "It's almost like we destroyed their GPS so they couldn't find the highways. [...] The cells just sat there and didn't move."
Metastasis and cell movement
Metastasis is a complex process with several stages. In each, certain conditions must be met before the cancer can progress.
For instance, during invasion of neighboring tissue, both the tumor cells and their microenvironment, or extracellular matrix, undergo major changes.
Most cells have some ability to move through the extracellular matrix that surrounds them, thanks to a complex feedback of cues known as contact guidance.
Scientists have observed this guidance in various settings, such as in wound healing and the generation and regeneration of organs.
Dr. Provenzano and his team say that contact guidance also helps cancer cells to sense and follow pathways in tumors. They liken the patterns of guidance to "highways" for cancer cell invasion.
Survival rates tend to be lower in people who have tumors with a lot of these patterns.
The authors of the new study note that the medical community has yet to fully understand how cancer cells sense contact guidance cues.
Engineered tumor microenvironments
To investigate how the cells recognize and follow these pathways, the team engineered 2-D microenvironments that mimic patterns of guidance cues in tumors.
Working with engineered environments greatly speeds up this kind of research.
"By using these controlled network microenvironments, we were able to test hundreds of cell movement events in hours, compared to one or two in the same time frame by imaging a tumor," explains first study author Dr. Erdem D. Tabdanov, who also works in the university's biomedical engineering department.
The following short video from the University of Minnesota shows what happened when the researchers used drugs to target the motor-like movements of breast cancer cells. The cells switched to a flowing, ooze-like movement that relies on different mechanisms.
The team intends to test their method on other types of cancer, then start trials in animals. If these go well, trials in humans should follow within a few years.
Researchers also need to investigate other aspects of the approach, such as the effect on healthy cells.
"Ultimately, we'd like to find ways to suppress cancer cell movement while enhancing immune cell movement to fight the cancer."
Dr. Paolo P. Provenzano