January 18, 2012
Protein Assists The Spread Of Breast Cancer
Researchers have uncovered a protein that helps some breast cancer tumors to break through their surrounding cell matrix and spread to other tissues.
The protein, called hepsin, is a protease which is a class of enzymes that cuts other proteins. Proteases can be successfully targeted by drugs, providing the opportunity to target hepsin as a possible new treatment.
Co-author Zena Werb, PhD, a professor of anatomy at University of California - San Francisco, 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.”
The researchers studied mouse mammary glands and tissue fragments, called organoids. They found when the tumor suppressor gene liver kinase B1 (Lkb1) was inactivated parts of the mammary gland developed abnormally. The basement membrane, a closely knit matrix of protein fibers was also found to be damaged.
The researchers suspected hepsin to be the cause of the basement membrane destruction, which caused the tumors to become unbound. When they deactivated the hepsin, the basement membrane recovered from the damage.
The scientists then re-engineered their mice by leaving out the Lkb1 gene. Hepsin then spread and the basement membrane was damaged but there were no resulting tumors.
Normally Lkb1 regulates the spread of hepsin over the cell membrane. When the Lkb1 is removed hepsin spreads uncontrollably blanketing the surface of cells causing destruction of basement membrane.
Johanna Partenen, a University of Helsinki graduate student said, “I was disappointed with the results. However, then I realized that although broken basement membrane may give cells more freedom to proliferate, the cells may just lay there, resting, and not start to over-proliferate unless they are pushed into cycles of cell division.”
The mice were again re-engineered to activate the gene Myc, which helps to initiate tumor growth. They soon saw tumor growth in the mice.
The research findings are published in the January 16, 2012 edition of the Proceedings of the American Academy of Sciences.
Image Caption: 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. Credit: UCSF
On the Net:
- University of California - San Francisco
- University of Helsinki
- Proceedings of the American Academy of Sciences