(Press-News.org) Scientists from The University of Manchester working with IBM Research have identified a key biological mechanism that for the first time explains why women with dense breast tissue are at greater risk of developing breast cancer.
The research, published today in the journal Cell Cycle, has important implications for future cancer prevention and treatment.
Women with higher breast density—detected on mammograms—have more compacted breast tissue and are more likely to develop breast cancer, but until now the reasons for this have been unclear.
Manchester scientists, funded by leading UK research organization Breakthrough Breast Cancer, worked with IBM researchers and academics in the USA and Cyprus to uncover the biological mechanisms at play. Their findings could help to improve breast cancer prevention by targeting these specific biological mechanisms with cancer therapies in at-risk patients and could potentially lead the way for a new strategy for the use of preventative treatments.
Professor Michael Lisanti, from The University of Manchester, part of Manchester Cancer Research Centre, said, "We know that high breast density can greatly increase a woman's breast cancer risk as well as other factors such as aging, family history, and presence of mutations in genes such as BRCA 1 and BRCA 2.
"What no one has fully appreciated before are the underpinning mechanisms at play. Using a bioinformatics approach, we have identified the relevant signaling pathways that make dense breast tissue more favorable for tumor formation.
"This signaling pathway could be used as a biomarker to identify women at higher risk of breast cancer more accurately and earlier than the current methods. Furthermore, there are drugs out there that block these pathways, so that these women could be offered effective chemoprevention."
The researchers used structural cells, called fibroblasts, from high-density breast tissue to generate a molecular signature. This signature showed that a cellular communication network called JNK1 was activated to a greater extent in fibroblasts from high-density breast tissue. The JNK1 network is known to instruct cells to release chemicals that create an inflammatory environment, and inflammation is known to be a driver of tumor formation.
The study team explained that blocking the JNK1 network could feasibly reduce the risk of, and potentially prevent, breast cancer in women with high density breast tissue. Interestingly, the molecular signature of the fibroblasts isolated from high density tissue also matched the fibroblasts found in breast tumors, meaning drugs that interfere with the JNK1 network could also potentially act as a treatment for women who already have breast cancer.
Dr Federica Sotgia, from The University of Manchester's Institute of Cancer Sciences and joint-senior author on the paper, said, "This research expands on the early work by the London surgeon Stephen Paget, who proposed the 'seed and the soil' hypothesis, now over 125 years ago. In this paradigm, the 'seeds' are the cancers cells and the 'soil' is the tissue in which they grow.
"Our research has identified the right soil for seeds to flourish by looking at the microenvironment in the breast and examining the mechanisms at play. This can help us with designing new preventative trials, to develop and test new therapies, which might prevent progression on to cancer.
"Current cancer treatment often focuses on targeting cancer cells but is not focused on targeting the fibrotic connective tissue, that may develop first, before you have cancer."
The researchers now plan to team up with other world-leading experts in cancer signaling based in Manchester including Professor Nic Jones, Director of MCRC and Cancer Research UK Chief Scientist who heads the Cell Regulation Laboratory, which studies how cells respond to sudden adverse changes in their surroundings, known as environmental stress. They will also team up with Professor Tony Howell who specializes on breast density.
Aristotelis Tsirigos, computational biology researcher from IBM, said, "These results are very exciting. It suggests a new pathway to target in the microenvironment for cancer cells." Scientists at the Computational Biology Center in IBM Research provided analytics tools and performed analysis of the data to help tease out the biological mechanisms at play in studying the micro-environment of breast cancer cells. As biological data is becoming more abundant and available, data-driven analytics methods and high-performance computing systems are becoming more useful in suggesting novel hypotheses for life sciences experiments and discovery.
Professor Howell, based at the Genesis Breast Cancer Prevention Centre at University Hospital of South Manchester, and at The University of Manchester, said, "At least 50 per cent of cancer risk is genetic, but activated cell stress signaling could potentially be reduced by dietary or lifestyle intervention. This research should help with a cancer prevention strategy, rather than waiting to treat the cancer once it arrives."
Professor Jones said, "This analysis of breast density provides a new framework for additional experimental exploration in breast cancer research. This has important clinical and translational implications for stratified medicine and breast cancer prevention."
INFORMATION:
The paper entitled "JNK1 stress signaling is hyper-activated in high breast density and the tumor stroma: Connecting fibrosis, inflammation, and stemness for cancer prevention" is published in Cell Cycle on 15th February 2014 and is available online now at https://www.landesbioscience.com/journals/cc/article/27379/.
About The University of Manchester
The University of Manchester, a member of the Russell Group, is one of the largest and most popular universities in the UK. It has 20 academic schools and hundreds of specialist research groups undertaking pioneering multi-disciplinary teaching and research of worldwide significance. According to the results of the 2008 Research Assessment Exercise, The University of Manchester is one of the country's major research institutions, rated third in the UK in terms of "research power." The University has an annual income of £807 million and is ranked 40th in the world and fifth in the UK for the quality of its teaching and impact of its research.
About Breakthrough Breast Cancer
Breakthrough Breast Cancer is the UK's leading breast cancer charity dedicated to saving lives through improving early diagnosis, developing new treatments and preventing all types of the disease.
The need for Breakthrough Breast Cancer's work has never been greater. Breast cancer is the most common of all cancers in the UK, with 50,000 women diagnosed every year and 1,000 women dying every month.
Breast cancer is not yesterday's problem; it's a disease that affects more women every year. Breakthrough Breast Cancer is working harder than ever before to stop women getting, and dying from, the disease.
The charity funds 25% of the breast cancer research in the UK, campaigns to ensure survival rates are among the best in the world and educates women to recognise the signs and symptoms of the disease. Breakthrough Breast Cancer's vision is a world freed from breast cancer.
For more information go to breakthrough.org.uk
Twitter: @BreakthroughBC / Facebook: Breakthrough Breast Cancer / YouTube: Breakthrough Breast Cancer
About IBM
For more information on IBM Research visit http://www.research.ibm.com.
About Landes Bioscience
In addition to the cell cycle and cell division, Cell Cycle covers all topics from man to virus, from DNA to RNA, from aging to development, from cell senescence to stem cells, from apoptosis to autophagy, from cancer to neurobiology, from molecular and theoretical biology to medicine and therapy. Established in 1997, Landes Bioscience is an Austin, Texas-based publisher of biology research journals and books. For more information on Landes Bioscience, please visit http://www.landesbioscience.com/.
New study explains how dense breast tissue drives the early stages of cancer
2014-02-12
ELSE PRESS RELEASES FROM THIS DATE:
Strong religious beliefs may drive self-perception of addiction to online pornography
2014-02-12
People who consider themselves very religious and view Internet porn even once may perceive they are addicted, according to a new Case Western Reserve University's psychology study.
"This is one of the first studies to examine the link between perceptions of addiction to online pornography and religious beliefs," said Joshua Grubbs, a doctoral student in psychology and lead author of the study.
The research, "Transgression as Addiction: Religiosity and Moral Disapproval as Predictors of Perceived Addiction to Pornography," will be published today in the journal, Archives ...
Helping preserve independent living
2014-02-12
This news release is available in German. Mr. S. is visually impaired and dependent on a cane since suffering a stroke. Nevertheless, as a 70-yr old living alone, he would rather not move into a care home. Most older people harbor this wish. They want to stay in their own familiar surroundings and continue to live independently for as long as possible. According to data from the German Federal Statistical Office, this applies to 70 percent of seniors. Against better judgment, they are putting their health at risk, for not only does the risk of cardiovascular problems ...
Male Pinterest users are more interested in art than cars
2014-02-12
Male users of Pinterest pin more content about photography, art, design, and home decor than sports, technology and cars, says a new study by researchers at the University of Minnesota and Georgia Tech.
The study revealed that while women and men differed in the types of content they collected and the degree to which they specialized, surprisingly men were not particularly interested in stereotypically male topics.
The most popular topics on Pinterest tend to be of "traditional female" interest including food and drink, crafts, home decor, and women's fashion. While ...
Weight loss program for infrared cameras
2014-02-12
This news release is available in German. We want it cozy and warm in our homes when the thermometer outside gets down into the minus area. Especially with older buildings, however, the money we pay for heat ends up out the window. The fault lies hidden in incorrect insulation, or at spots around windows or ceiling joints that are not sealed. These weak points cannot be perceived from outside – unless you are viewing the building though the lens of an infrared camera. This type of camera is equipped with specialized sensors that distinguish the temperature differences ...
From surf to turf: Archaeologists and chemists trace ancient British diets
2014-02-12
The change by our ancestors from hunter-gathers to farmers is one of the most intensively researched aspects of archaeology. Now a large-scale investigation of British archaeological sites dating from around 4,600 BC to 1,400 AD has examined millions of fragments of bone and analysed over 1,000 cooking pots.
The team, led by Professor Richard Evershed of the University of Bristol's School of Chemistry, developed new techniques in an effort to identify fish oils in the pots. Remarkably, they showed that more than 99 per cent of the earliest farmer's cooking pots lacked ...
Prostate cancer advance could improve treatment options
2014-02-12
Researchers at the University of East Anglia have made an important advance in understanding genetic changes associated with terminal prostate cancer.
Findings published today in the British Journal of Cancer, and funded by the Association for International Cancer Research (AICR), show how a genetic mutation in untreated patients is linked to aggressive cancer later in life. It was previously thought that the mutation only occurred in response to therapy.
The research highlights why relapses could occur in some men following hormone therapy. And it could help identify ...
Mountains, models, salt, sand, and cycles
2014-02-12
Boulder, Colo., USA – Topics in this current batch of Geology articles posted ahead of print include the puzzle of parallel mountain chains; 25 years on the East Pacific Rise; unique episodes in Earth's history; turbidity currents; computer models; Wilson cycles; salt structure beneath the sea bed; the North Scotia Ridge; El Hierro, Canary Islands; sand-sized sub-spherical silica grains; bank pull or bar push; kaolinitic paleosols; Earth's youngest, hottest rocks; 3-D thermo-mechanical numerical models; and the Bohemian Massif.
Open Access Papers:
1. Sublithospheric ...
Filling me softly
2014-02-12
Surgical implants are widely used in modern medicine but their effectiveness is often compromised by how our bodies react to them. Now, scientists at the University of Cambridge have discovered that implant stiffness is a major cause of this so-called foreign body reaction.
This is the first time that stiffness of implant materials has been shown to be involved in foreign body reactions. The findings – published in the journal Biomaterials – could lead to major improvements in surgical implants and the quality of life of patients whose lives depend on them.
Foreign ...
The physics of curly hair
2014-02-12
CAMBRIDGE, Mass-- The heroes and villains in animated films tend to be on opposite ends of the moral spectrum. But they're often similar in their hair, which is usually extremely rigid or — if it moves at all — is straight and swings to and fro. It's rare to see an animated character with bouncy, curly hair, since computer animators don't have a simple mathematical means for describing it.
However, change may be coming soon to a theater near you: In a paper appearing in the Feb. 13 issue of Physical Review Letters, researchers at MIT and the Université Pierre et Marie ...
Test for persistent Lyme infection using live ticks shown safe in clinical study
2014-02-12
In a first-of-its-kind study for Lyme disease, researchers have used live, disease-free ticks to see if Lyme disease bacteria can be detected in people who continue to experience symptoms such as fatigue or arthritis after completing antibiotic therapy. The technique, called xenodiagnosis, attempts to find evidence of a disease-causing microbe indirectly, through use of the natural disease-carrier—in this case, ticks. It was well tolerated by the volunteers, but investigators could not find evidence of Lyme disease bacteria in most of the cases where enough ticks were collected ...