How Malignant Skin Cancer Spreads to Other Areas of the Body

Following an announcement voicing success in eliminating melanoma metastasis in laboratory experiments, researchers at Virginia Commonwealth University have made another important discovery. They now have a clearer understanding of the process by which a specific gene (mda-9/syntenin) aids in the development of metastasis in melanoma and possibly in a number of other cancers.

Published in Cancer Research, the study shows that mda-9/syntenin is a key regulator of angiogenesis, the process that leads to the synthesis of new blood vessels in tumors. Study lead author, Paul Fisher, M.Ph., Ph. D., originally cloned the gene in his laboratory.

Fisher claims, "Our research brings us one step closer to understanding precisely how metastatic melanoma, a highly aggressive and therapy-resistant cancer, spreads throughout the body. 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 found that the mda-9/syntenin gene controls the expression of several proteins responsible for stimulating angiogenesis, including the compounds insulin growth factor binding protein-2 (IGFBP-2) and interleukin-8 (IL-8).
In in vivo and in vitro experiments, the researchers confirmed that mda-9/syntenin binds with the extracellular matrix (ECM) to spark a series of chemical pathways that eventually results in endothelial cells secreting IGFBP-2.

The extracellular matrix is the substance that cells secrete and in which they are embedded. Endothelial cells line the interior surface of blood vessels throughout the entire circulatory system. When IGFBP-2 is secreted, endothelial cells begin to produce and secrete vascular endothelial growth factor-A, a protein that regulates the development of and creation of new blood vessels.

Fisher concludes, "This is a major breakthrough in understanding angiogenesis and its impact in melanoma metastasis. 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."


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