UCSF Team Blocks Enzyme That Contributes to the Spread of Breast Cancer

A research team may have discovered a means to prevent breast cancer from spreading to other parts of the body through the blocking of a single enzyme.

Scientists from the University of California, San Francisco (UCSF) found that blocking an enzyme known as MMP9 could be the key. At least, so far that has been the case in mouse models. The enzyme, the researchers found, is an “essential component” in the “cancer's metastasis-promoting machinery.” MMP9 provides the means for the cancer cells to form new metastatic tumors. By blocking the enzyme, the researchers believe that it could be a revolutionary advance in immuno-oncology treatments.

Vicki Plaks, an assistant adjunct professor in the Department of Orofacial Sciences at UCSF and the co-leader of the research team, said that when the team began to examine lung tissue in their mouse model, they found that MMP9 was a key to “remodeling” healthy tissue and making it more accessible to cancer cells. When the cancer cells colonize these sites with the help of MMP9, they're able to start growing into new tumors, the researchers said.

“Metastasis is the biggest hurdle when it comes to successfully treating breast cancer and solid tumors in general. Once a cancer becomes metastatic, there's really no cure, and the only option is to manage it as a chronic disease,” Plaks said in a statement.

Data from the study was published this week in the journal Life Science Alliance. The study suggests that the metastases can be stopped before they begin to develop through the administration of an antibody that specifically targets and disrupts MMP9 activity. The researchers found that interfering with MMP9 helped “recruit and activate cancer-fighting immune cells” to metastatic sites. It’s that result that could have important implications for treating certain types of metastatic breast cancer with immunotherapy.

Plaks said the work indicates a combination approach of immunotherapy with antibodies targeting MMP9 activity may have some success in treating metastatic breast cancers of the luminal B type, which was the type the UCSF team focused on in its studies.

However, the scientists discovered that disrupting the enzyme only affects the spread of the cancer and not the primary tumor. The researchers speculate that the enzyme’s primary role, at least in the cancer scenario, is “helping existing malignancies metastasize.”

Before this latest study, the UCSF team found that that MMP9 plays an “important role in remodeling the extracellular matrix (ECM),” which is a group of molecules that provide “structure and shape” organs and also help cells communicate with each other. The ECM also plays a role in promoting cellular health, the team discovered. While MMP9 was known to be involved in cancer, the team said its role in the earliest stages of metastasis had not been fully explored. The first hint that MMP9 might be involved in early-stage metastasis came from publicly available gene expression data from clinical breast cancer biopsies. When they examined this data, the researchers discovered that MMP9 levels were elevated in metastatic disease.