Scientists from the University of Granada and GENYO (Pfizer-University of Granada-Andalusian Government Center for Genomics and Oncological Research), in a study led by Juan Carlos Rodríguez-Manzaneque, demonstrated the important role of a protein called ADAMTS1 in uveal melanoma, one of the rarest and most aggressive cancers that exists, which develops in the eye.
Tumors are made up not only of a mass of cells that grow uncontrollably, but also of the environment they create as they grow, together creating what is called the “tumor microenvironment.” . In this environment, there are proteins that remodel it, called extracellular proteases, which are able to inhibit or contribute to tumor growth and metastasis, by modifying the non-cellular elements of the tumor microenvironment that form the so-called extracellular matrix.
In this study, published in the journal Cancers, researchers investigated the role that one of these proteases, ADAMTS1, plays in the development of a rare and very aggressive subtype of melanoma: uveal melanoma. Uveal melanoma develops in the eye, although 50% of patients develop metastases, and it has an incidence of 2 to 8 cases per million population in Europe.
“In this research, we demonstrated that the ADAMTS1 protease is necessary for cancer cells to mimic endothelial cells (responsible for blood vessel formation), which is linked to more aggressive tumors and a poorer clinical prognosis.” , explains Carlos Peris Torres, the main author of the work.
To do this, the researchers inhibited the ADAMTS1 protease using CRISPR / Cas9 gene editing technology. It is a molecular tool used to “edit” or “correct” the genome of any cell (its developers, Emmanuelle Charpentier and Jennifer A. Doudna, having won the Nobel Prize in chemistry this year). The researchers then verified the results of their intervention on the protease in in vitro models with cell lines, and in vivo with different mouse models.
In addition, using advanced bioinformatics tools and publicly available data on uveal melanoma (from the Cancer Genome Atlas Project, developed by the US National Cancer Institute, which has data on more than 20,000 samples from 33 different cancer types) , the UGR and GENYO scientists have discovered new genes whose expression affects the clinical prognosis of this type of tumor.
“These include several members of the ADAMTS family and endothelial genes such as CDH5 and KDR. Further analysis also revealed strong expression of ADAMTS1 in the early stages of uveal melanoma, which confirmed its contribution to the ‘initiation of tumor development and corroborated the results obtained experimentally, ”adds Peris Torres.
Based on these results, the researchers concluded that ADAMTS1 is necessary for the development of uveal melanoma. This study is also the first to support the development of therapeutic targets targeting the extracellular matrix to fight uveal melanoma.
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Carlos Peris-Torres et al. ADAMTS1 extracellular protease is required in the early stages of development of human uveal melanoma by inducing stem and endothelial-like features on tumor cells, Cancers (2020). DOI: 10.3390 / cancers12040801
Quote: Scientists demonstrate role of protein called ADAMTS1 in rare eye cancer (2021, January 15) retrieved January 16, 2021 from https://medicalxpress.com/news/2021-01-scientists-role- protein-adamts1-rare.html
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