University of California San Francisco
Helen Diller Family Comprehensive Cancer Center

Some Breast Cancer Spread May Be Triggered By Targetable Protein, Study Shows

By Jeffrey Norris | January 17, 2012

Some Breast Cancer Spread May Be Triggered By Targetable Protein, Study Shows

Scientists have identified a protein that cancer cells use to cut scaffolding that normally holds cells in place in the breast. Released from the scaffolding the cancer cells can spread to other tissues. In this electron microscope image of the mouse mammary gland, normal scaffolding, called the basement membrane, appears on the right. On the left, the membrane is degraded, and one cell (white arrow) can be seen bulging out.

Cancers rarely are deadly unless they evolve the ability to grow beyond the tissues in which they first arise. Normally, cells — even early-stage tumor cells — are tethered to scaffolding that helps to restrain any destructive tendencies. But scientists from the University of Helsinki, Finland, and from UCSF have identified a cleaver-wielding protein that frees some tumor cells, allowing them to further misbehave.

The protein, they discovered, often blankets the surface of breast tumor cells and can help untether the cells from the matrix of their native tissue. Once released, they may continue to expand their numbers into other tissues where their normal counterparts do not tread.

The protein, called hepsin, is a protease, a class of enzymes that cleaves, or cuts, other proteins. Proteases have been targeted successfully by drugs, and hepsin presents a new possible drug target, the researchers said.

“If we could delay or prevent a tumor from switching from one that grows in place to one that invades, then that would be a major milestone in cancer treatment,” said study co-author Zena Werb, PhD, a professor of anatomy at UCSF. Werb has for decades studied the ways in which the behavior of tumor cells is influenced by their surroundings, with a focus on breast tumors.

Working with mouse models of breast development and breast cancer in Werb’s UCSF laboratory during a visiting professorship, University of Helsinki scientist Juha Klefström, PhD along with Johanna Partanen, a University of Helsinki graduate student — designed and led experiments that resulted in the discovery of the hepsin protein’s role.

Their findings are published in the Jan. 16, 2012 edition of the Proceedings of the American Academy of Sciences (PNAS).

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