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Cellular "highways" reveal mechanisms of melanoma

Anton Buzdin, researcher from Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences together with colleagues from China, the USA and Switzerland used a new type of biomarkers – molecular pathways that have helped to trace the development of skin cancer: from normal to malignant tumors. Based on it scientists created a melanoma diagnosis system in its early stages. The article was published in "Oncotarget" magazine.

molecular pathways, melanoma, skin cancer, OncoFinder

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Melanoma is a type of skin cancer causing 3.5 thousand deaths in Russia annually. Melanoma forms secondary tumors – metastasis – and cause 80% of all deaths in skin cancer. Initially tumor arises from melanocytes, i.e. the pigment cells, which protect the skin from ultraviolet radiation. Then tumor cells acquire the ability to spread through the lymphatic and blood vessels, often falling into the bones, lungs, liver and brain.

Immunohistochemistry is considered one of the most accurate diagnostic methods to identify tumor antigens. The method helps to detect pathologically reversed proteins associated with cancer development. But it is possible to investigate only a relatively small amount of protein markers that strongly affect the success of the diagnosis. The scientists’ published study found a way to analyze a few thousands at once.

– We have investigated a new type of biomarkers – molecular pathways. Using such paths, metabolic and signaling, the process of regulation of all major interactions within cells is occurring. And it includes malignant tumors’ development, – Anton Buzdin says, head of Group for Genomic Regulation of Cell Signaling Systems Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences, one of the authors of the article. – We have analyzed the activity of these pathways to study the differences in detail and possible transition from benign tumors to malignant and further – to the metastatic tumor.

Scientists took 500 samples of  melanoma, moles and normal skin. Gene activity data was processed through OncoFinder program previously developed by the same team. The program helped to quantify the activity of a plurality of molecular pathways in the samples. This work permitted determination the "footprints" of the various forms of melanoma.

– As a result of the analysis we found molecular pathways that perfectly mark the transition from normal cell to a mole, and then – to melanoma. It revealed that the processes may vary: for melanoma cells formed from a mole they are one, and for melanoma from normal skin cells – others, – Anton Buzdin explains. – And we have learned that the molecular pathways have a number of previously unknown cases of joint regulation. It means that they cooperate, unite into broader regulatory and metabolic networks.

According to the researchers this information will help to identify tumors’ vulnerable places on the molecular level and therefore will allow picking up new therapies for the treatment of this serious illness.

Read more: “Molecular pathway activation features linked with transition from normal skin to primary and metastatic melanomas in human

april 12, 2016