Navigation Links
Some breast cancer spread may be triggered by a protein, study shows
Date:1/17/2012

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 Klefstrm, 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 January 16, 2012 edition of the Proceedings of the American Academy of Sciences (PNAS).

The scientists studied mammary glands in mice and tissue fragments called organoids isolated from these glands.

They found that inactivation of a tumor suppressor gene known as liver kinase B1 (Lkb1) caused abnormal development of parts of the mammary gland, including milk-secreting structures. Specifically, they determined that a tightly knit matrix of protein fibers called the basement membrane -- which normally surrounds the milk-secreting structures -- was damaged and degraded.

These events may be triggered in many tumors, the team said, as they found that Lkb1 was abnormally missing in 1 out of every 4 human breast cancer samples they looked at.

Most solid tumors arise from "epithelial" cells, which line the surfaces and cavities of organs. The basement membrane, in turn, lines epithelial cell layers in tissues.

In their mouse studies, the researchers quickly settled on hepsin as a suspect in the destruction of the basement membrane that in turn allows tumor cells to become unbound. In the absence of Lkb1, the protein-cleaving enzyme was abnormally spread over the cell surface. They found that deactivating hepsin allowed the basement membrane to recover.

Graduate student Partanen sought to recapitulate the development of cancer by re-engineering the mice, knocking Lkb1 out of normal mammary epithelial cells. Again, hepsin spread abnormally and basement membrane proteins were sliced and diced. After a year, though, she found that the mice had not grown mammary tumors.

"I was disappointed with the results," she said. "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."

Partanen then re-engineered the mice so that they also abnormally activated a gene called Myc, which, is known to help initiate tumors in many tissues, including breast epithelium. She soon saw the mice begin to form tumors.

"We found in our study that genetic removal of hepsin from the mammary gland organoids prevents formation of cancerous tissue," Klefstrm said. "This finding excites us, as it leads us to think that inhibition of hepsin by drug-like molecules could restrain cancer progression.

"However, we do not know yet if we can cure already-formed tumors by blocking hepsin activity. We need to first improve our experimental systems to properly address this question."

According to Web, "We have observed that loss of Lkb1, combined with activation of a weak inducer of breast cancer an oncogene such as Myc can produce aggressive cancers.

"In humans, breast cancers that have diminished amounts of Lkb1 show strong hepsin expression. Since hepsin sits on the cell membrane, it should be accessible to drugs. We believe that hepsin forms a novel target for treatment of a subset of breast cancer patients."


'/>"/>
Contact: Jeffrey Norris
jeffrey.norris@ucsf.edu
415-502-6397
University of California - San Francisco
Source:Eurekalert  

Related biology news :

1. Researchers identify possible receptor for key breast cancer regulator
2. ISG15: A novel therapeutic target to slow breast cancer cell motility
3. Cell-CT: A new dimension in breast cancer research
4. Breastfeeding promotes healthy growth
5. Breastfeeding saved babies in 19th century Montreal
6. MRI may be noninvasive method to measure breast cancer prognosis
7. New Achilles heel in breast cancer: Tumor cell mitochondria
8. USC researchers discover key aspect of process that activates breast cancer genes
9. HDAC inhibitor may overcome resistance to common breast cancer drug
10. Benefit of novel drug in breast cancer seen in blood within weeks
11. Signaling pathway linked to inflammatory breast cancer may drive disease metastasis
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Some breast cancer spread may be triggered by a protein, study shows
(Date:2/3/2016)... , February 3, 2016 ... new market research report "Automated Fingerprint Identification System Market ... Latent Search), Application (Banking & Finance, Government, Healthcare, and ... by MarketsandMarkets, the market is expected to be worth ... of 21.0% between 2015 and 2020. The transformation and ...
(Date:2/2/2016)... 2016 Checkpoint Inhibitors for Cancer – ... Are you interested in the future of cancer ... inhibitors. Visiongain,s report gives those predictions to 2026 ... level. Avoid falling behind in data or ... revenues those emerging cancer therapies can achieve. There ...
(Date:2/1/2016)... NEW YORK , Feb. 1, 2016  Today, ... Heart Association (AHA) announced plans to develop a first ... cognitive computing power of IBM Watson. In the first ... disease, AHA, IBM (NYSE: IBM ), and Welltok ... metrics and health assessments with cognitive analytics, delivered on ...
Breaking Biology News(10 mins):
(Date:2/11/2016)... ... February 11, 2016 , ... ... cutting-edge information focused on the development and manufacture of biopharmaceuticals and therapeutics, ... sponsor of the 2016 BioProcess International Awards – Recognizing Excellence in the ...
(Date:2/11/2016)... --  BioInformant announces the February 2016 release of ... Tools, and Technologies – Market Size, Segments, Trends, and ... The first and only market research ... has more than a decade of historical information on ... cell type. This powerful 175 page global strategic report ...
(Date:2/11/2016)... , ... February 11, 2016 , ... ... its new stem cell treatment clinic in Quito, Ecuador. The new facility will ... trauma applications to patients from around the world. , The new GSCG ...
(Date:2/10/2016)...  The Maryland House of Delegates and House Speaker ... of Maryland School of Medicine Dean E. Albert ... Medical System President and CEO Robert Chrencik , ... honor given to the public by the leader of ... and Mr. Chrencik for their contributions to our ...
Breaking Biology Technology: