University of California San Francisco
Helen Diller Family Comprehensive Cancer Center

Researchers Halt Spread of Breast Cancer by Blocking Metastasis-Promoting Enzyme

Findings in Mice Point to New Approach That May Help Make Some Metastatic Breast Cancers Susceptible to Immunotherapy

By Jason Alvarez | | November 14, 2019

Researchers Halt Spread of Breast Cancer by Blocking Metastasis-Promoting Enzyme

In a breakthrough with important implications for the future of immunotherapy for breast cancer, UC San Francisco scientists have found that blocking the activity of a single enzyme can prevent a common type of breast cancer from spreading to distant organs.

While studying a mouse model that replicates key features of early-stage human breast cancer, the researchers discovered that a ubiquitous enzyme called MMP9 is an essential component of the cancer’s metastasis-promoting machinery, helping to create a hospitable environment for itinerant cancer cells to form new metastatic tumors.

“Metastasis is the biggest hurdle when it comes to successfully treating breast cancer, and solid tumors in general,” said Vicki Plaks, PhD, now an assistant adjunct professor in the department of orofacial sciences at UCSF. “Once a cancer becomes metastatic, there’s really no cure, and the only option is to manage it as a chronic disease.” Plaks co-led the team that made the discovery when still a postdoctoral fellow in the laboratory of Zena Werb, PhD, a professor of anatomy and associate director for basic science at the UCSF Helen Diller Family Comprehensive Cancer Center.

When they examined lung tissue in their mouse model, the researchers found that MMP9 is involved in remodeling healthy tissue and transforming it into a kind of safe haven for migrating breast cancer cells. When the cancer cells colonize these sites with the help of MMP9, they’re able to start growing into new tumors.

The new study, published Nov. 14 in the journal Life Science Alliance, shows that these metastases can be stopped before they are able to lay the foundations for tumor growth. By administering an antibody that specifically targets and disrupts MMP9 activity, the scientists were able to prevent cancer from colonizing the lungs of mice. But interestingly, interfering with MMP9 had no effect on the primary tumor, which suggests that the enzyme’s primary role in this scenario is helping existing malignancies metastasize and colonize other organs rather than promoting the growth of established primary tumors.