Enzyme Treatment Strips Mucins from Cancer Cells

Researchers at Stanford University have developed a new type of cancer therapy. The technology targets mucins, sugar-coated proteins that help cancer cells to metastasize and avoid the immune system. In particular, mucins enable cancer cells to survive free-floating as they travel through the blood during metastasis and can also trick immune cells into assuming that the cancer cell is not a threat. The new treatment involves combining an enzyme called mucinase with a cancer-specific nanobody that can bind to the cell surface, allowing the mucinase to destroy any mucins present. In tests with mice with simulated breast and lung cancer, the treatment significantly reduced tumor growth and enhanced survival.     

Cancer cells employ a variety of tricks to ensure their survival and growth. One involves mucins, a common sugar-coated protein that is found on the surface of many cell types. “Mucins play important roles throughout the body, such as forming mucus in our gut and lungs, and protecting us from pathogens,” said Gabrielle Tender, a researcher involved in the study. “Cancers dial this natural process up to 11, hijacking the functions of mucins to protect themselves and spread throughout the body.”

In cancer cells, mucins assist in allowing the cell to live as it floats freely through the blood vessels and finds a new site to create a metastatic tumor. Ordinarily, cells from solid tumors are more accustomed to surviving within a solid tissue mass, so this role for mucins is crucial in metastasis. Mucins also act as camouflage against the immune system, helping cancer cells to evade destruction.

Mucins are ubiquitous within the body, and so don’t represent a good drug target on their own. However, by combining a bacterially derived mucinase, an enzyme that can cleave mucins off the cell surface, with a cancer-targeting nanobody, the researchers ensured that their treatment would not target healthy cells.

So far, in tests with mice with simulated lung and breast cancer, the treatment successfully slowed tumor growth and enhanced mouse survival. “We have decades of evidence from cancer patients and experiments that mucins are important in cancer, but there was not that much that we could previously do to get rid of these mucins,” said Tender. “We were inspired that we finally have an approach to degrade mucins on cancer cells.”    

Study in journal Nature Biotechnology: Design of a mucin-selective protease for targeted degradation of cancer-associated mucins

Via: Stanford University