Some breast cancer spread may be triggered by a protein, study shows
This electron microscope image shows normal basement membrane in mouse mammary epithelium on the right. On the left side the membrane is degraded, and one cell (white arrow) can be seen bulging out. Credit: UCSF
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 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," Klefström 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."
Provided by University of California, San Francisco
- Breast cancer: How tumor cells break free and form metastases Jul 04, 2008 | not rated yet | 0
- Team identifies new breast cancer tumor suppressor and how it works Jun 27, 2011 | not rated yet | 0
- 'Cancer prognosis gene' found to control the fate of breast cells Nov 30, 2006 | not rated yet | 0
- 'Innocent bystanders' can be the cause of tumor development Mar 03, 2008 | not rated yet | 0
- Gene helps protect tumor suppressor in breast cancer Apr 06, 2009 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013 Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
In recent years, microRNAs (miRNAs) and other non-coding RNAs are small molecules that help control the expression of specific proteins. In recent years they have emerged as disease biomarkers. miRNA profiles have been used ...
Cancer 6 hours ago | not rated yet | 0
Cancer cells spread and grow by avoiding detection and destruction by the immune system. Stimulation of the immune system can help to eliminate cancer cells; however, there are many factors that cause the immune system to ...
Cancer 6 hours ago | not rated yet | 0
Researchers from London's Kingston University have begun a two-year study which could help prolong the lives of people with colorectal tumours.
Cancer 9 hours ago | 5 / 5 (1) | 0
Transformative research from Western University has identified new hormones in the body which may suppress breast cancer and stimulate the regression of breast tumors.
Cancer 10 hours ago | 5 / 5 (1) | 0
(Medical Xpress)—Curtin University researchers have found evidence that targeting specific cells in the body can reverse the effects of cancer on the immune system.
Cancer 10 hours ago | 5 / 5 (3) | 0
Two mutations central to the development of infantile myofibromatosis (IM)—a disorder characterized by multiple tumors involving the skin, bone, and soft tissue—may provide new therapeutic targets, according to researchers ...
4 hours ago | 5 / 5 (1) | 0 |
(Medical Xpress)—A new study by researchers in the US has shown that an ancient virus can be modified to help in the fight against the simian immunodeficiency virus SIV, which is the equivalent in monkeys ...
9 hours ago | 5 / 5 (3) | 0 |
Talking on a hands-free device while behind the wheel can lead to a sharp increase in errors that could imperil other drivers on the road, according to new research from the University of Alberta.
3 hours ago | not rated yet | 0
Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.
6 hours ago | 5 / 5 (1) | 0 |
Biological processes are generally based on events at the molecular and cellular level. To understand what happens in the course of infections, diseases or normal bodily functions, scientists would need to ...
7 hours ago | 5 / 5 (2) | 0 |
Kate O'Reilly's spring allergy survival kit includes the usual stuff - nasal sprays, allergy pills and a box of tissues. This season, she's added a new weapon to her line of defense: an app on her smartphone.
4 hours ago | not rated yet | 0