Tissue around tumor holds key to fighting triple negative breast cancer
A natural substance found in the surrounding tissue of a tumor may be a promising weapon to stop triple negative breast cancer from metastasizing.
A preclinical study published in PLOS ONE September 19 by Thomas Jefferson University researchers found that decorin, a well-studied protein known to help halt tumor growth, induces a series of tumor suppressor genes in the surrounding tissue of triple negative breast cancer tumors that help stop metastasis.
"These findings provide a new paradigm for decorin, with great implications for curbing tumor growth by inducing new tumor suppressor genes within the tumor microenvironment, and for the discovery of novel gene signatures that could eventually help clinical assessment and prognosis," said senior author Renato V. Iozzo, M.D., Professor of Pathology, Anatomy and Cell Biology, at Thomas Jefferson University.
Triple negative breast cancer is the most deadly of breast cancers, with fast-growing tumors, that disproportionately affect younger and African-American women. Today, no such marker is applied in care of triple negative breast cancer, and as a result, patients are all treated the same.
"Originally, we thought that decorin was affecting the tumor, but, surprisingly, decorin affects the so-called tumor microenvironment, where malignant cells grow and invade, igniting genes to stop such growth," said Dr. Iozzo, who is also a member of Jefferson's Kimmel Cancer Center. "Absence of decorin in the microenvironment could explain metastasis in some patients, where higher levels of the protein may keep cancer from spreading."
In the study, 357 genes were found to be induced by the increased presence of decorin, but more interestingly, the researchers discovered that three of these genes, which were previously unlinked to triple negative breast cancer, were tumor suppressor genes affecting the tumor microenvironment, including Bmp2K, Zc3hav1, and PEG3.
Decorin is a naturally occurring substance in the connective tissue where, among other roles, it helps regulate cell growth by interacting with growth factors and collagen. A decade ago, Dr. Iozzo and his team discovered that decorin, a cell protein, and specifically, a proteoglycan, is increased in the matrix surrounding tumor cells. They also discovered that decorin causes production of a protein, p21, which also can arrest cell growth. However, decorin's role in breast cancer and the mechanism behind its anti-tumor properties remained elusive.
For this study, researchers aimed to investigate the impact of decorin in triple negative breast cancer tumors using human cell lines in mice, as well analyze gene expression activity in the tumor microenvironment.
Tumors treated with decorin were found to have a decreased volume of up to 50 percent after 23 days. Using a sophisticated microarray technique, the researchers then analyzed the mouse tumor microenvironment, finding increased expression of 357 genes, three of which are the tumor suppressor genes of interest.
These results demonstrate a novel role for decorin in reduction or prevention of tumor metastases that could eventually lead to improved therapeutics for metastatic breast cancer.
"Here, we have a molecule that can turn a tumor microenvironment from a bad neighborhood to a clean neighborhood by inducing genes in that neighborhood to stop growth and prevent the tumor from metastasizing," said Dr. Iozzo.
More information: dx.plos.org/10.137… pone.0045559
Journal reference: PLoS ONE
Provided by Thomas Jefferson University
- SABCS: Loss of RB in triple negative breast cancer associated with favorable clinical outcome Dec 09, 2011 | not rated yet | 0
- In vitro study identifies potential combination therapy for breast cancer Jul 02, 2012 | not rated yet | 0
- Breaking the backbone of triple-negative breast cancers Mar 19, 2012 | not rated yet | 0
- Study reveals how normal cells fuel tumor growth Dec 21, 2011 | not rated yet | 0
- New suppressor of common liver cancer Dec 15, 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
How can there be villous adenoma in colon, if there are no villi there
17 hours ago 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...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
- More from Physics Forums - Medical Sciences
More news stories
(HealthDay)—The American Cancer Society, which is celebrating on Wednesday a century of fighting a disease once viewed as a death sentence, is making a pledge to put itself out of business.
Cancer 7 hours ago | not rated yet | 0
National Lung Screening Trial (NLST) investigators also conclude that the 20 percent reduction in lung cancer mortality with low-dose computed tomography (LDCT) versus chest X-ray (CXR) screening previously reported in the ...
Cancer 7 hours ago | not rated yet | 0
Researchers have developed a new drug delivery system that allows inhalation of chemotherapeutic drugs to help treat lung cancer, and in laboratory and animal tests it appears to reduce the systemic damage ...
Cancer 11 hours ago | not rated yet | 0 |
When turned on, the gene p53 turns off cancer. However, when existing drugs boost p53, only a few tumors die – the rest resist the challenge. A study published in the journal Cell Reports shows how: tumors that live even i ...
Cancer 11 hours ago | not rated yet | 0 |
Study leader, Professor John Mathews from the University of Melbourne said this small increase in cancer risk must be weighed against the undoubted benefits from CT scans in diagnosing and monitoring disease.
Cancer 15 hours ago | not rated yet | 0
Existing research shows that bicyclists who wear helmets have an 88 percent lower risk of brain injury, but researchers at Boston Children's Hospital found that simply having bicycle helmet laws in place showed a 20 percent ...
50 minutes ago | not rated yet | 0
Swiss scientists reveal the mechanism responsible for aging hidden deep within mitochondria—and dramatically slow it down in worms by administering antibiotics to the young.
11 hours ago | 4.9 / 5 (7) | 0 |
Researchers from Queen Mary, University of London have led the largest sequencing study of human disease to date, investigating the genetic basis of six autoimmune diseases.
11 hours ago | 4 / 5 (1) | 0 |
Until now, little was scientifically known about the human potential to cultivate compassion—the emotional state of caring for people who are suffering in a way that motivates altruistic behavior.
8 hours ago | 5 / 5 (2) | 2 |
(HealthDay)—Migraines and depression can each cause a great deal of suffering, but new research indicates the combination of the two may be linked to something else entirely—a smaller brain.
8 hours ago | 4 / 5 (2) | 0 |
A new approach for immunizing against influenza elicited a more potent immune response and broader protection than the currently licensed seasonal influenza vaccines when tested in mice and ferrets. The vaccine ...
9 hours ago | not rated yet | 0 |