Corporate Banner
Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

MicroRNAs can Convert Normal Cells into Cancer Promoters

Published: Friday, November 23, 2012
Last Updated: Friday, November 23, 2012
Bookmark and Share
Study pinpoints new targets for ovarian cancer treatment.

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."

The Ovarian Cancer Research Fund supported this study. Additional authors include Anirban Mitra, Marion Zillhardt and Payal Tiwari from the University of Chicago, and Youjia Hua and Andrea Murmann from Northwestern University.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,000+ scientific posters on ePosters
  • More than 4,400+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.


Scientific News
Cell Transplant Treats Parkinson’s in Mice
A University of Wisconsin—Madison neuroscientist has inserted a genetic switch into nerve cells so a patient can alter their activity by taking designer drugs that would not affect any other cell.
Understanding Female HIV Transmission
Glowing virus maps points of entry through entire female reproductive tract for first time.
Genetic Markers Influence Addiction
Differences in vulnerability to cocaine addiction and relapse linked to both inherited traits and epigenetics, U-M researchers find.
A lncRNA Regulates Repair of DNA Breaks in Breast Cancer Cells
Findings give "new insight" into biology of tough-to-treat breast cancer.
Detection of HPV in First-Void Urine
Similar sensitivity of HPV test on first void urine sample compared to cervical smear.
Shape Of Tumor May Affect Whether Cells Can Metastasize
Illinois researchers found that the shape of a tumor may play a role in how cancer cells become primed to spread.
Computational Model Finds New Protein-Protein Interactions
Researchers at University of Pittsburgh have discovered 500 new protein-protein interactions (PPIs) associated with genes linked to schizophrenia.
MicroRNA Pathway Could Lead to New Avenues for Leukemia Treatment
Cancer researchers at the University of Cincinnati have found a particular signaling route in microRNA (miR-22) that could lead to targets for acute myeloid leukemia, the most common type of fast-growing cancer of the blood and bone marrow.
Analysis of Dog Genome will Provide Insight into Human Disease
An important model in studying human disease, the non-coding RNA of the canine genome is an essential starting point for evolutionary and biomedical studies – according to a new study led by The Genome Analysis Centre (TGAC).
New Insights into Gene Regulation
Researchers have solved the three-dimensional structure of a gene repression complex that is known to play a role in cancer.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,400+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!