After recently announcing success in eliminating melanoma metastasis in laboratory experiments, scientists at Virginia Commonwealth University Massey Cancer Center have made another important discovery in understanding the process by which the gene mda-9/syntenin contributes to metastasis in melanoma (the spread of skin cancer) and possibly a variety of other cancers.
Published in the journal Cancer Research, the study demonstrated that mda-9/syntenin is a key regulator of angiogenesis, the process responsible for the formation of new blood vessels in tumors. Mda-9/syntenin was originally cloned in the laboratory of the study's lead author Paul B. Fisher, M.Ph., Ph.D., Thelma Newmeyer Corman Endowed Chair in Cancer Research and program co-leader of Cancer Molecular Genetics at Virginia Commonwealth University Massey Cancer Center, chairman of VCU's Department of Human and Molecular Genetics and director of the VCU Institute of Molecular Medicine.
"Our research brings us one step closer to understanding precisely how metastatic melanoma, a highly aggressive and therapy-resistant cancer, spreads throughout the body," says Fisher. "Additionally, analysis of the human genome has indicated that mda-9/syntenin is elevated in the majority of cancers, which means novel drugs that target this gene could potentially be applicable to a broad spectrum of other deadly cancers."
Fisher's team discovered that mda-9/syntenin regulates the expression of several proteins responsible for promoting angiogenesis, including insulin growth factor binding protein-2 (IGFBP-2) and interleukin-8 (IL-8). The study is the first to provide proof of the pro-angiogenic functions of IGFBP-2 in human melanoma.
In in vivo and in vitro experiments, the scientists confirmed that mda-9/syntenin binds with the extracellular matrix (ECM) to start a series of biological processes that eventually cause endothelial cells to secrete IGFBP-2. The ECM is the substance that cells secrete and in which they are embedded. Endothelial cells are the cells that line the interior surface of blood vessels throughout the entire circulatory system. The secretion of IGFBP-2, in turn, caused the endothelial cells to produce and secrete vascular endothelial growth factor-A (VEGF-A), a protein that mediates the development of and formation of new blood vessels.
The researchers also noted that IGFBP-2 could potentially serve as a novel biomarker to monitor for disease progression in melanoma patients.
"This is a major breakthrough in understanding angiogenesis and its impact in melanoma metastasis," says Fisher. "We are now focusing on developing novel small molecules that specifically target mda-9/syntenin and IGFBP-2, which could be used as drugs to treat melanoma and potentially many other cancers."
Virginia Commonwealth University: http://www.vcu.edu
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
For the first time, researchers have tracked the spread of Ebola, almost in real time, during an outbreak. The virus is quickly changing its DNA. But it's still unclear what these mutations mean.
Think of all the adults you know. Think of your parents and grandparents. Think of the teachers you had at school, your doctors and dentists, the people who collect your rubbish, and the actors you see on TV. All of these people probably have little mites crawling, eating, sleeping, and having sex on their faces.
A trial vaccine against Ebola could be tested on healthy volunteers in the UK in September, says an international health consortium.
The ALS Association has raised more than $94 million in recent weeks via its online ice bucket challenge — compared with $2.7 million this time last year. Now what?
Implant attached to bone in pioneering technique that helps prevent infection and discomfort
A new method for removing allergens from peanuts means help could soon be on the way for the roughly 2.8 million Americans with a potentially life-threatening allergy to the popular food, the U.S. Department of Agriculture said on Tuesday.
Survey finds many social media users hesitate to express opinions unless they know their followers will agree with them
Ebola has a nasty reputation for damaging the body, especially its blood vessels. But when you look at the nitty-gritty details of what happens after a person is infected, a surprising fact surfaces.
You think bringing a new toothbrush to market is easy? The seven-year saga of two dental entrepreneurs struggling to bring their patented brush to consumers suggests otherwise.
Scholars have long tried to understand how culture affects communities. New research argues that the parking behavior of drivers may tell us something about the economic productivity of nations.