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.
The story of the vaccines development is just one part of a rich and intertwined history of scientific discovery and controversy
A highly sensitive blood test for Ebola exists, so why isn't it being used to test all returning health workers from West Africa? Because the virus isn't in the blood in the first stages of infection.
Drinking beverages enriched with compounds found in cocoa beans improved older adults' performances on a memory test – but there's a catch
A 700-year-old caribou dropping from northern Canada holds surprisingly well-preserved viruses. There's no evidence the viruses are dangerous, but they are scientifically interesting.
The New England Journal of Medicine published an editorial against quarantining people who have worked with Ebola patients in Africa. Renee Montagne speaks with Dr. Lindsey Baden, one of the authors.
Surgeons in Australia say they have performed the first heart transplant using a "dead heart".
Ebola underlines the urgent need for a new way of responding to global epidemics, say Harvey Rubin and Nicholas Saidel
As researchers from Africa to China to America race to develop vaccines and treatments to fight Ebola, health experts are grappling with the economics of a disease that until this year had been off the drug industry's radar.
Is California's severe drought hurting the nutrient content of fruit? No, preliminary data on pomegranates suggest. The fruit may be smaller, but packed with more antioxidants, tests show.
The Food and Drug Administration has issued warning letters to companies marketing products claimed to be cures for Ebola. One firm says it will drop such claims — but it's still selling the product.