Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Mechanical forces driving breast cancer lead to key molecular discovery

28.03.2014

UCSF scientists say new finding could lead to more accurate prognosis

The stiffening of breast tissue in breast-cancer development points to a new way to distinguish a type of breast cancer with a poor prognosis from a related, but often less deadly type, UC San Francisco researchers have found in a new study.

The findings, published online March 16, 2014 in Nature Medicine, may lead eventually to new treatment focused not only on molecular targets within cancerous cells, but also on mechanical properties of surrounding tissue, the researchers said.

In a mouse model of breast cancer, scientists led by Valerie Weaver, PhD, professor of surgery and anatomy and director of the Center for Bioengineering and Tissue Regeneration at UCSF, identified a biochemical chain of events leading to tumor progression. Significantly, this chain of events was triggered by stiffening of scaffolding tissue in the microscopic environment surrounding pre-cancerous cells. The stiffening led to the production of a molecule that can be measured in human breast cancer tissue, and which the researchers found was associated with worse clinical outcomes.

... more about:
»Medicine »UCSF »biochemical »breast »subtypes »tumors

"This discovery of the molecular chain of events between tissue stiffening and spreading cancer may lead to new and more effective treatment strategies that target structural changes in breast cancers and other tumors," Weaver said.

In the mouse experiments, Janna Mouw, PhD, a UCSF associate specialist who works in Weaver's lab, found that tissue stiffening in microscopic scaffolding known as the extracellular matrix, or ECM, increases signaling by ECM-associated molecules, called integrins. The integrins in turn trigger a signaling cascade within cells that leads to the production of a tumor-promoting molecule called miR-18a.

Unlike most cellular signaling molecules thus far studied by scientists, miR-18a is not a protein or a hormone, but rather a microRNA, another type of molecule recognized in recent years to play an important role in the lives of cells. The miR-18a dials down the levels of a protective, tumor-suppressing protein called PTEN, which often is disabled in cancerous cells, leading to abnormal biochemical signaling that can promote cancer growth.

Stiffening of the tissue microenvironment in tumors

Weaver is a trained biochemist, and has been a trailblazer in the study of tissue mechanics and cancer for 15 years. Mouw is a mechanical engineer. The newly reported UCSF discovery highlights the importance of mechanical forces in the development of cancer, which usually is thought of in biochemical terms.

Armed with modern lab techniques, Weaver has made many discoveries about the mechanical and structural properties of tumor tissue and the stiffening that can occur. For example, she was the first to identify the cross-linking of structural elements within the ECM as a precursor to cancer progression.

Her research team's latest findings are of clinical interest because they may lead to earlier identification of certain difficult-to-treat breast cancers. About 60 percent of breast cancers can be easily identified as a type known as luminal breast cancer, but there are two subtypes of luminal breast cancer that are difficult to distinguish.

Luminal A breast cancer accounts for about 40 percent of all breast cancers, while luminal B breast cancer comprises about 20 percent. On average, women with luminal B breast cancer do not survive as long after treatment without breast cancer recurring, and they are less likely to respond to hormone therapies such as tamoxifen. Lack of a good diagnostic tool results in overtreatment of many luminal A breast cancers, Weaver said.

According to Shelley Hwang, MD, PhD, chief of breast surgery at Duke University Hospital, former UCSF faculty member and a clinical collaborator for the Nature Medicine study, "Current methods for distinguishing luminal A breast cancer from luminal B breast cancer are expensive and time consuming, and are rarely used in medical practice." If a link between miR18a and luminal B breast cancer can be definitively confirmed, and if a reliable clinical laboratory test can be developed to measure miR18a in the tumor tissue, it would provide a practical way to distinguish the two tumor subtypes, Hwang said.

Laura Van't Veer, head of the breast oncology program at the Helen Diller Family Comprehensive Cancer Center at UCSF, and the developer of MammaPrint, a 70-gene test used to predict breast cancer spread, said the Nature Medicine study represents a major finding.

"The work provides early evidence that miR18a is a strong predictor of metastasis and poor survival in women with luminal breast tumors, and that it may be used to distinguish luminal A breast tumors from luminal B breast tumors," Van't Veer said.

###

Additional co-authors of the study include Yoshihiro Yui, Laura Damiano, Russell Bainer, Johnathon Lakins, Irene Acerbi, Guanqing Ou, Amanda Wijekoon, and Yunn-Yi Chen from UCSF; Kandice Levental from the University of Texas, Houston; and Penney Gilbert from the University of Toronto. The study was funded by the US Department of Defense Breast Cancer Research Program, Susan G. Komen and the National Institutes of Health.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy, a graduate division with nationally renowned programs in basic biomedical, translational and population sciences, as well as a preeminent biomedical research enterprise and two top-ranked hospitals, UCSF Medical Center and UCSF Benioff Children's Hospital.

Jeffrey Norris | EurekAlert!

Further reports about: Medicine UCSF biochemical breast subtypes tumors

More articles from Health and Medicine:

nachricht Proteomics and precision medicine
08.02.2016 | University of Iowa Health Care

nachricht Scientists create imaging 'toolkit' to help identify new brain tumor drug targets
02.02.2016 | eLife

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The most accurate optical single-ion clock worldwide

Atomic clock experts from the Physikalisch-Technische Bundesanstalt (PTB) are the first research group in the world to have built an optical single-ion clock which attains an accuracy which had only been predicted theoretically so far. Their optical ytterbium clock achieved a relative systematic measurement uncertainty of 3 E-18. The results have been published in the current issue of the scientific journal "Physical Review Letters".

Atomic clock experts from the Physikalisch-Technische Bundesanstalt (PTB) are the first research group in the world to have built an optical single-ion clock...

Im Focus: Goodbye ground control: autonomous nanosatellites

The University of Würzburg has two new space projects in the pipeline which are concerned with the observation of planets and autonomous fault correction aboard satellites. The German Federal Ministry of Economic Affairs and Energy funds the projects with around 1.6 million euros.

Detecting tornadoes that sweep across Mars. Discovering meteors that fall to Earth. Investigating strange lightning that flashes from Earth's atmosphere into...

Im Focus: Flow phenomena on solid surfaces: Physicists highlight key role played by boundary layer velocity

Physicists from Saarland University and the ESPCI in Paris have shown how liquids on solid surfaces can be made to slide over the surface a bit like a bobsleigh on ice. The key is to apply a coating at the boundary between the liquid and the surface that induces the liquid to slip. This results in an increase in the average flow velocity of the liquid and its throughput. This was demonstrated by studying the behaviour of droplets on surfaces with different coatings as they evolved into the equilibrium state. The results could prove useful in optimizing industrial processes, such as the extrusion of plastics.

The study has been published in the respected academic journal PNAS (Proceedings of the National Academy of Sciences of the United States of America).

Im Focus: New study: How stable is the West Antarctic Ice Sheet?

Exceeding critical temperature limits in the Southern Ocean may cause the collapse of ice sheets and a sharp rise in sea levels

A future warming of the Southern Ocean caused by rising greenhouse gas concentrations in the atmosphere may severely disrupt the stability of the West...

Im Focus: Superconductivity: footballs with no resistance

Indications of light-induced lossless electricity transmission in fullerenes contribute to the search for superconducting materials for practical applications.

Superconductors have long been confined to niche applications, due to the fact that the highest temperature at which even the best of these materials becomes...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Travel grants available: Meet the world’s most proficient mathematicians and computer scientists

09.02.2016 | Event News

AKL’16: Experience Laser Technology Live in Europe´s Largest Laser Application Center!

02.02.2016 | Event News

From intelligent knee braces to anti-theft backpacks

26.01.2016 | Event News

 
Latest News

About injured hearts that grow back - Heart regeneration mechanism in zebrafish revealed

10.02.2016 | Life Sciences

The most accurate optical single-ion clock worldwide

10.02.2016 | Earth Sciences

Absorbing acoustics with soundless spirals

10.02.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>