Navigation Links
NYU Langone Medical Center researchers find micro RNA plays a key role in melanoma metastasis

NEW YORK CITY (February 5, 2009)Scientists have long wondered how melanoma cells travel from primary tumors on the surface of the skin to the brain, liver and lungs, where they become more aggressive, resistant to therapy, and deadly. Now, scientists from NYU Langone Medical Center have identified the possible culprita short strand of RNA called microRNA (miRNA) that is over-expressed in metastatic melanoma cell lines and tissues.

The new findings, published online this week and in the February 10, 2009 print edition of the Proceedings of the National Academy of Sciences (PNAS), suggest that miRNA silencing to counteract or attack this mechanism may be an effective therapeutic strategy for metastatic melanoma, according to Eva Hernando, Ph.D., assistant professor in the Department of Pathology at NYU School of Medicine, and the lead author of the study. Dr. Hernando is also a member of the NYU Cancer Institute at NYU Langone Medical Center.

The highly aggressive character of melanoma, says Dr. Hernando, makes it an excellent model to probe the mechanisms underlying metastasis, the process by which cancer cells travel from the primary tumor to distant sites in the body. Though other researchers have found that altered miRNAs contribute to breast cancer metastasis, this is the first study to examine the role of miRNA in metastatic melanoma.

"Melanoma becomes deadly after the cells leave the primary tumor through the blood and metastasize in other organs where they are resistant to therapy," says Dr. Hernando, who notes that the average survival for patients after melanoma metastasis occurs is only nine months. "Normal cells are unable to travel and survive in alien locations, so we are very interested in understanding the invasive, adaptive, and resistant traits of the very aggressive melanoma cell." miRNAs are short pieces of RNA that block the expression of proteins that are encoded by messenger RNAs. They serve as regulators of protein expression, acting like the volume control on a radio. In recent years, miRNAs have been linked to the over- or under-expression of a variety of genes linked to cancer and other diseases.

Dr. Hernando's lab found a miRNA is over-expressed in metastatic melanoma cell lines and tissues. The lab found that the elevated expression of miRNA 182 turns it into an oncogene (a gene involved in cancer tumor initiation or progression), by increasing the invasive capacity of melanoma cells in vitro and stimulating the cell's metastatic potential in a mouse model.

In addition, the NYU scientists found that miRNA 182 also represses the expression of two tumor suppressors called FOXO3 and MITF, which normally prevent cells from becoming malignant. By repressing the suppressors, miRNA 182 permits melanoma cells to migrate and survive independently, two properties necessary for metastasis.

MiRNA 182 also belongs to a cluster located in a genomic region, chromosome 7q, that is frequently amplified in melanoma and contains two other oncogenes; BRAF and C-MET. The study found a correlation between genomic amplification and miRNA over expression, though it is unclear whether other molecular mechanisms play a role in this effect, according to Dr. Hernando.

Finally, the scientists observed that in a significant fraction of metastatic melanomas, high miRNA 182 levels correlate with low levels of FOXO3 and MITF, supporting the relevance of this mechanism in human melanoma.

The study suggests that miRNA 182 is a novel therapeutic target. When it is inhibited, it impairs the invasive potential of melanoma cells and induces cell death. In theory, the administration of anti-miRNA 182 could block the growth or expansion of the primary melanoma tumor. Several academic laboratories and pharmaceutical companies are working to improve the delivery of anti-miRNAs by using chemical modification and nano particles to increase their stability, specificity, and ability to reach tumors in sufficient doses with low toxicity.

The NYU Cancer Institute is currently studying whether anti-miRNA will work on miRNA 182 to inhibit the growth or spread of primary melanoma in mice. Dr. Hernando says that even if the anti-miRNA cannot do this on its own, it might work in combination with conventional chemotherapy or novel targeted therapies.

This study is the result of an extensive collaboration between members of NYU's Interdisciplinary Melanoma Cooperative Group, led by Iman Osman, M.D. , one of the study's co-authors, which has a large biospecimen bank comprising human tissue, blood and patient clinico-pathological information.

"The existence of this bank permits us to validate our laboratory findings using human tissue," says Dr. Hernando. "In this study, we began looking at cell lines and then at melanoma tissue. Now that the mechanism has been proven using cell lines and mice, the next step will be to perform in-vitro studies with cell lines to assess the effect of anti-miRNA on cell death in both normal and melanoma cells. Once that study is completed, we can use this model for studies in mice to block the growth of the primary melanoma tumor or the metastasis by using anti-miRNA. All these steps will determine if this approach could be eventually applied to humans."


Contact: Nadine Woloshin
NYU Langone Medical Center / New York University School of Medicine

Related biology news :

1. NYU Langone Medical Centers tip sheet to the International Conference on Alzheimers Disease 2008
2. Fluorescent proteins illuminating biomedical research
3. Texas Medical Center researchers win collaborative grants
4. Key to future medical breakthroughs is systems biology, say leading European scientists
5. First images from medical beamline at Canadian Light Source
6. Biomedical researchers create artificial human bone marrow in a test tube
7. University of Miami biomedical engineer
8. Biomedical research profits from the exploration of the deep sea
9. Biomedical engineers detective work reveals antibiotic mechanism
10. New book helps medical students master clinical skills
11. TECNALIA investigates advanced biomaterials to make more reliable and hardwearing medical implants
Post Your Comments:
(Date:5/9/2016)... 2016 Elevay is currently known ... freedom for high net worth professionals seeking travel for ... connected world, there is still no substitute for a ... sealing your deal with a firm handshake. This is ... advantage of citizenship via investment programs like those offered ...
(Date:4/26/2016)... India and LONDON ... Infosys Finacle, part of EdgeVerve Systems, a product ... and Onegini today announced a partnership to integrate ... solutions.      (Logo: ... to provide their customers enhanced security to access ...
(Date:4/15/2016)... 2016 Research and Markets has ... Market 2016-2020,"  report to their offering.  , ... ,The global gait biometrics market is expected to ... period 2016-2020. Gait analysis generates multiple ... used to compute factors that are not or ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... June 23, 2016 Houston Methodist Willowbrook ... Cy-Fair Sports Association to serve as their official ... Houston Methodist Willowbrook will provide sponsorship support, athletic ... with association coaches, volunteers, athletes and families. ... Cy-Fair Sports Association and to bring Houston Methodist ...
(Date:6/23/2016)... -- The Biodesign Challenge (BDC), a university competition that asks ... systems and biotechnology, announced its winning teams at the ... York City . The teams, chosen ... MoMA,s Celeste Bartos Theater during the daylong summit. Keynote ... of architecture and design, and Suzanne Lee , ...
(Date:6/23/2016)... ... June 23, 2016 , ... STACS DNA Inc., the sample tracking software ... State Crime Laboratory, has joined STACS DNA as a Field Application Specialist. , ... Tremblay, President and COO of STACS DNA. “In further expanding our capacity as a ...
(Date:6/23/2016)... Calif. , June 23, 2016  Blueprint Bio, ... biological discoveries to the medical community, has closed its ... Matthew Nunez . "We have received ... with the capital we need to meet our current ... essentially provide us the runway to complete validation on ...
Breaking Biology Technology: