Navigation Links
MicroRNAs can convert normal cells into cancer promoters
Date:11/21/2012

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 microRNAssmall 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."


'/>"/>

Contact: John Easton
john.easton@uchospitals.edu
773-795-5225
University of Chicago Medical Center
Source:Eurekalert

Related medicine news :

1. Pint-size microRNAs show promise against weighty problem, researchers say
2. Device converting images into music helps individuals without vision reach for objects in space
3. Documenting womens experiences with chromosome abnormalities found in new prenatal test
4. Abnormal carotid arteries found in children with kidney disease
5. Double drug combo could shut down abnormal blood vessel growth that feeds disease
6. Overweight Teens Typically Eat Less Than Normal-Weight Peers
7. Overweight Teens Typically Eat Less Than Normal-Weight Peers
8. Even High-Normal Blood Sugar Tied to Brain Shrinkage
9. Normal weight individuals with belly fat at highest CVD risk
10. People of normal weight with belly fat at highest death risk, Mayo Clinic study
11. Normal-Weight People With Type 2 Diabetes Have Higher Death Risk: Study
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/2/2016)... ... 2016 , ... Mediaplanet is proud to announce the launch ... innovative treatments, therapeutic technologies, and revolutionized nutrition that are helping patients and physicians ... years in the last 3 decades,” says Dr. Valentine Fuster, a world-renowned cardiologist. ...
(Date:12/2/2016)... ... December 02, 2016 , ... ... diagnostic imaging systems and the first company to offer robotic imaging to ... at their tradeshow booth # 941 for the American Association of Equine Practitioners ...
(Date:12/2/2016)... ... 2016 , ... Yisrayl Hawkins, at The House of Yahweh in Abilene, Texas, ... Bible Prophecy. Yisrayl says this generation, known as the Last Generation, started in 1934 ... details line up exactly with Bible Prophecy – a protected way for those who ...
(Date:12/2/2016)... ... 02, 2016 , ... On November 24th, 2016, Thanksgiving morning, ... different sites throughout Miami-Dade and Broward counties. This is the largest meal delivery ... Thanksgiving morning by putting together individual meals via assembly lines and passing them ...
(Date:12/2/2016)... ... December 02, 2016 , ... ‘Tis the season for giving! Today, 20 ... the National Family Partnership and the Drug Enforcement Administration as part of the National ... the 10 winning schools who decorated their campuses with this year’s Red Ribbon Week ...
Breaking Medicine News(10 mins):
(Date:12/2/2016)... , December 2, 2016 ... "In Vitro Diagnostics/IVD Market by Product (Instruments, Reagents, ... Application (Diabetes, Oncology, Cardiology, Nephrology, Infectious Diseases) - ... market is valued at USD 60.22 Billion in ... a CAGR of 5.5% during the forecast period ...
(Date:12/2/2016)... 2, 2016 On Thursday, December ... excellence in research, development and innovation in the biopharmaceutical ... was held in the presence of Sergey Tsyb, Vice ... Russian Federation , Natalia Sanina, First Vice Chairman ... , Head of Roszdravnadzor, National Service of Control in ...
(Date:12/2/2016)... 2, 2016 bioLytical Laboratories, ein Weltführer bei schnellen ... Mitgliedern des Apothekenbundes von Kenia eingeführt. Continue ... ... HIV Self Test! (PRNewsFoto/bioLytical Laboratories) ...      (Photo: http://photos.prnewswire.com/prnh/20161201/444905 ) bioLytical wurde ...
Breaking Medicine Technology: