Stopping cancer metastasis by preventing tumor movement

A new study shows how researchers stopped cancer cells from moving and spreading, even when the cells changed their movements. The discovery could have a major impact on millions of people undergoing therapies to prevent the spread of cancer within the body.

Researchers have known for years that tumors have patterns that are like little "highways" that cancer cells use to move within the tumors and ultimately toward blood vessels and adjacent tissue to invade the body. Patients who have high numbers of these patterns in their tumors have a lower chance of surviving the cancer.

What the researchers haven't been able to figure out until now is how the cells recognize these patterns and move along them.

In this study, the team examined in the lab how breast cancer cells moved and used medicines to try to stop the cells. When they stopped the mechanisms that serve as the motor of the cells, the cells surprisingly changed the way they moved to an oozing-like motion, almost like a blob.

"Cancer cells are very sneaky," said senior author. "We didn't expect the cells to change their movement. This forced us to change our tactics to target both kinds of movements simultaneously. It's almost like we destroyed their GPS so they couldn't find the highways. This stopped the cells in their tracks. The cells just sat there and didn't move."

Ninety percent of cancer deaths are due to the cancer spreading throughout the body. Putting the brakes on cancer cell movement would allow physicians the time to use other therapies to improve survival rates of patients.

The researchers studied the cells in the lab in two-dimensional, engineered microenvironments, that are almost like a microchip with cells. Authors used a platform with variable stiffness that facilitates uniaxial or biaxial matrix cues, or competing E-cadherin adhesions to demonstrate distinct mechanoresponsive behavior. These microenvironments mimicked how the cells behave as they do in a tumor and allowed researchers to speed up their research.

Authors show that inn contractile cells, guidance sensing is strongly dependent on formins and FAK signaling and can be perturbed by disrupting microtubule dynamics, while low traction conditions initiate fluidic-like dendritic protrusions that are dependent on Arp2/3. Concomitant disruption of these bimodal mechanisms completely abrogates the contact guidance response.

"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," said the first author of the study.

The next steps for the research team are to expand the types of cancers studied and begin animal trials. Within a few years, the researchers hope to move to clinical trials in humans. They will also study how the medicines interact and what side effects may result.

"Ultimately, we'd like to find ways to suppress cancer cell movement while enhancing immune cell movement to fight the cancer," the senior author said.

https://twin-cities.umn.edu/news-events/researchers-stop-sneaky-cancer-cells-their-tracks