A new mechanism has been discovered to ‘starve’ tumors. It is a new protein variant, expressed only by tumor blood vessels, which contributes to making the cancer more aggressive and therefore represents a new tumor marker and a possible molecular target. The discovery comes from a study, supported by the Italian Cancer Research Association (Airc), and conducted at the Institute of Molecular Genetics of the Cnr of Pavia. The results, published in the journal Nature Communications, thus provide important new information to make therapeutic approaches more effective.
“The growth of tumors – explains Claudia Ghigna, of the ‘Luigi Luca Cavalli Sforza’ Institute of Molecular Genetics of the Cnr of Pavia (Cnr-Igm), who directed the study, conducted in collaboration with several Italian research centers and universities and international – is 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 ”.
The research – explains a Cnr-Igm note – shows how, through the mechanism known as ‘alternative splicing’, blood vessel cells produce a new variant of the UNC5B protein never described before, called UNC5B- 8. “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 starting from the same initial template ”, continues Ghigna. “The research findings turn the spotlight on the still little known 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. “Angiogenesis, however, 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.
“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 mechanisms More information on the blood vessels that nourish the tumor is therefore essential to make these therapeutic approaches more effective. In this study we found that the new protein variant UNC5B-8 is produced solely by blood vessel cells and preferentially by those associated with more aggressive tumors and with 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-8 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-8, has an 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 ”, concludes Pradella.