Breast Cancer TME Stiffness May Promote Metastasis

Researchers from the University of Arizona have found that the stiffness of the breast tumor microenvironment can cause changes to cancer cells that make them more aggressively spread to the bone. The scientists also developed a novel mechanical conditioning score, used to quantify cellular changes. Their findings were published in Cell Reports. 

"Unfortunately, bone metastasis is normally not identified until an advanced state when it's not reversible," said senior author Ghassan Mouneimne. "What's really exciting is one day being able to take a sample from the patient's primary tumor and predict who is at high risk for bone metastasis. Then we could intervene with a prevention strategy that we are now validating in the lab."

The team created a laboratory environment that mimicked the stiff or soft tumor environments encountered in the body and assessed how breast cancer cells responded. They found that cells grown in a stiff environment had a "mechanical response" characterized by cell spreading, invasion, and turning on genes linked with both bone development and disease. And these gene changes endured even after the cells were moved to a soft environment.

Next, researchers looked at what genes were turned on and off in breast cancer cells in response to the stiff environments. Based on these gene expression changes, they developed a MeCo score, which was then validated and refined using data from thousands of patients with breast cancer.