It is a protein variant expressed only on the surface of tumor blood vessels which contributes to making the cancer more aggressive and represents
a new tumor marker and a possible molecular target
In a study directed by Claudia Ghigna, of the Luigi Luca Cavalli-Sforza Institute of Molecular Genetics of the National Research Council of Pavia (Cnr-Igm), in collaboration with several Italian and international research centers and universities, a new protein variant expressed only on the surface of tumor blood vessels. The results of the study, supported by the AIRC Foundation for Cancer Research, were published in Nature Communications. “This new variant helps make cancer more aggressive and represents a new tumor marker and possible molecular target,” explains the researcher. “The growth of tumors is in fact closely related to the nutrients supplied by the blood vessels associated with the tumor: limiting the development of the latter therefore represents a possible therapeutic strategy to ‘starve’ the tumor and make it more susceptible to chemotherapy”. Research shows how, through the mechanism known as splicing alternativo, blood vessel cells produce a new variant of the UNC5B protein never described before, called UNC5B-D8. “Alternative splicing is a so-called ‘cut and sew’ mechanism, which allows the building blocks of human genes to be assembled in various ways and, as a consequence, to generate different proteins from the same initial template,” continues Ghigna. “The results of the research turn the spotlight on the still poorly understood role of alternative splicing in the development of tumor blood vessels.” The formation of blood vessels occurs through a process called angiogenesis and is essential for the different tissues and organs to receive the oxygen and nutrients necessary for their survival.
“However, angiogenesis is also decisive in tumor progression: from the earliest stages of development, cancer cells stimulate the formation of new vessels, thus supporting their growth and the formation of metastases in other organs or tissues”, explains the researcher of the Cnr-Igm. “From the study of angiogenesis, therapies have emerged that can stop or reverse the tumor, blocked in the formation of blood vessels and thus deprived of oxygen and nutrients. Unfortunately, so far, these therapies have shown modest results in patients, who often develop resistance mechanisms. More information on the blood vessels that feed the tumor is therefore crucial to making these therapeutic approaches more effective. In this study we found that the new protein variant UNC5B-D8 is produced solely by blood vessel cells and preferentially by those associated with more aggressive tumors with a less favorable prognosis. Therefore this variant offers an excellent diagnostic and prognostic tool, which could be exploited both as a new marker of tumor angiogenesis, and as a possible molecular target for more effective anti-cancer therapies “. “Driving the machine that generates the UNC5B-D8 protein is the NOVA2 factor”, concludes Davide Pradella, fellow at Cnr-Igm in Pavia thanks to a research grant supported by AIRC. ‘NOVA2, like UNC5B-D8, has altered expression in the blood vessels that feed the tumor, while it is absent or expressed at low levels in the blood vessels of healthy tissues. NOVA2 directly activates the alternative splicing of the UNC5B gene causing it to produce the new variant ».
August 28, 2021 (change August 28, 2021 | 11:33)
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