MicroRNAs can convert normal cells into cancer promoters
Unraveling the mechanism that ovarian cancer cells use to change normal cells around them into cells that promote tumor growth has identified several new targets for treatment of this deadly disease.
In the December issue of the American Association for Cancer Research journal Cancer Discovery, a team or researchers from the University of Chicago Medicine and Northwestern University Feinberg School of Medicine show that ovarian cancer cells induce nearby cells to alter their production of three microRNAs—small strands of genetic material that are important regulators of gene expression.
By changing gene expression, microRNAs can modify a cell's function. In this case, they convert normal, healthy fibroblasts into cancer-associated fibroblasts (CAFs). These CAFs pump out chemical signals telling cancer cells to multiply, invade healthy tissues and travel to distant sites in the abdomen. Importantly, by reversing the microRNA signals the researchers were able to cause CAFs to revert to normal fibroblasts.
"These cancer-supporting cells provide a novel and appealing treatment target," said one of the lead authors of the study Ernst Lengyel, MD, PhD, professor in the department of obstetrics and gynecology at the University of Chicago. "Cancer cells mutate rapidly, which enables them to develop drug resistance. But cancer-associated fibroblasts are genetically stable," he said. "Their harmful behavior is driven by the microRNAs. Inhibiting those signals is a new way to fight this disease. It disrupts the cancer's support system and is unlikely to evolve resistance."
"With ovarian cancer," Lengyel added, "we desperately need new treatments. "There have been no new approaches introduced into the clinic for years, and thus no major improvements in patient survival."
Fibroblasts are the primary cellular component of connective tissue. They provide the structural framework for other tissues and aid in wound healing. When fibroblast-dense tissues are infiltrated by cancer cells, however, "intimate cross-talk between fibroblasts and cancer cells" can covert them to cancer-associated fibroblasts, Lengyel said, "shifting them into a new role."
"Only a few years ago scientists learned how to reprogram normal cells into cells that can give rise to any cell type in the body," said the second lead author on the study Marcus Peter, PhD, professor of medicine at Northwestern University Feinberg School of Medicine. "Our work demonstrates that cancer cells also have the ability to reprogram cells in their environment into cells that support their growth and that this process involves microRNAs."
The researchers found that cancer cells caused normal fibroblasts to reduce production of two microRNAs, miR-31 and miR-214, and to increase production of miR-155. Since microRNAs usually block gene expression, reduced levels increased expression of several of their target genes. Many of those genes are involved in the production of the chemical signals associated with CAFs.
The most highly upregulated such signal, known as CCL5, is a "key tumor-promoting factor," the authors show. When human ovarian cancer cells and CAFs were co-injected into mice, the tumor cells soon replaced normal ovarian structures. Antibodies that neutralized CCL5 inhibited this augmented growth.
"One strength of our study is that we used tumor cells and CAFs from patients, rather than cell lines," said Lengyel, a gynecologic oncologist who specializes in the surgical treatment of women with ovarian cancer. "Our model system is as close as possible to the real situation."
"Therapeutic approaches targeting microRNAs in cancer cells are under development," added Peter. "Our work suggests that it might be possible to modify microRNA expression in cancer-associated fibroblasts for therapeutic benefit."
Journal reference: Cancer Discovery
Provided by University of Chicago Medical Center
- Ovarian cancer cells hijack surrounding tissues to enhance tumor growth Sep 04, 2012 | not rated yet | 0
- Fat cells in abdomen fuel spread of ovarian cancer Oct 30, 2011 | not rated yet | 0
- Mechanism for esophageal cancer uncovered Apr 11, 2011 | not rated yet | 0
- Infiltrating cancer's recruitment center Jan 26, 2011 | not rated yet | 0
- Researchers find possible key to regulation of ovarian cancer stem cells Sep 27, 2012 | 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
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...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
In a new study described in the journal Oncogene, researchers reveal how a key player in cell growth, immunity and the inflammatory response can be transformed into a primary contributor to tumor growth.
Cancer 2 hours ago | not rated yet | 0 |
A new study conducted using extensive medical records of over one million Israeli adolescents before military service shows clearly how exposure to the Israeli sun of young, light-skinned children increases substantially ...
Cancer 4 hours ago | not rated yet | 0
A new measure of the heterogeneity – the variety of genetic mutations – of cells within a tumor appears to predict treatment outcomes of patients with the most common type of head and neck cancer. In the May 20 issue ...
Cancer 8 hours ago | not rated yet | 0
Researchers at Mayo Clinic have developed a promising method to distinguish between pancreatic cancer and chronic pancreatitis—two disorders that are difficult to tell apart. A molecular marker obtained from pancreatic ...
Cancer 9 hours ago | not rated yet | 0
The use of a smartphone application significantly improves patients' preparation for a colonoscopy, according to new research presented today at Digestive Disease Week (DDW). The preparation process, which begins days in ...
Cancer May 19, 2013 | not rated yet | 0
A new study conducted by researchers at the Child Study Center at NYU Langone Medical Center found men diagnosed as children with attention-deficit/hyperactivity disorder (ADHD) were twice as likely to be obese in a 33-year ...
26 minutes ago | not rated yet | 0 |
A new computer model could help scientists predict when a particular strain of avian influenza might become infectious from bird to human, according to a report to be published in the International Journal Data Mining an ...
54 minutes ago | not rated yet | 0
Researchers at Lund University in Sweden have mapped the significance of heredity for common forms of atherosclerotic disease. No studies have previously examined whether different forms of the disease share heredity.
51 minutes ago | not rated yet | 0
A novel vaccine study from South Dakota State University (SDSU) will headline the groundbreaking research that will be unveiled at the American Association of Pharmaceutical Scientists' (AAPS) National Biotechnology Conference ...
3 minutes ago | not rated yet | 0
Parkinson's disease (PD) is a degenerative neurological disorder marked by a progressive loss of motor control. Despite intensive research, there are currently no approved therapies that have been demonstrated to alter the ...
3 minutes ago | not rated yet | 0
It is impossible to predict the evolution of China's human H7N9 bird flu outbreak as researchers are still trying to understand the source of human transmission, the head of the World Health Organisation said Monday.
33 minutes ago | not rated yet | 0