Scientists found the cause of aggressiveness of brain tumors

Scientists from BFU named after Immanuel Kant identified a molecular mechanism through which tumors, such as gliomas and neuroblastoma, become extremely aggressive and resistant to treatment. It turned out that increased urokinase PLAUR gene activity that regulates the remodeling of the extracellular substance promotes the appearance of metastases and the migration of tumor cells in the body. Evidence suggests that PLAUR may serve as a target for new antitumor drugs. The study is published in Advances in Molecular Oncology magazine.

Many tumors are able to metastasize — create new neoplastic lesions in the body due to cell migration. This is especially common for such aggressive cancers as gliomas and neuroblastoma that affect the brain and nerve tissue. It is very difficult to fight metastasis and recurrences of such tumors — surgical interventions, chemo-and radiotherapy are often powerless. In order to develop new effective methods of treatment that precisely target the tumor cells, we must acknowledge molecular targets that distinguish the tumor cells from healthy and propel their division and distribution. One of such possible targets is the urokinase receptor uPAR encoded by the gene PLAUR. Earlier studies have shown that high PLAUR gene activity is linked to tumor cells metastasis and poor patient prognosis. However, the exact molecular mechanisms underlying this relationship were not fully clear.

Scientists from Immanuel Kant Baltic Federal University (Kaliningrad) and Moscow state University named after M. V. Lomonosov (Moscow) examined cell lines of human glioma and neuroblastoma in order to study the impact of the PLAUR gene on tumor aggressiveness.

The authors have multiply increased the PLAUR gene activity in the investigated cells (by 3 and 20 times in U251 and U87 glioma cells accordingly; by 234 times in SH-SY5Y neuroblastoma cells) and found out that this lead to the launch of epithelial-mesenchymal transition — a process in which cells lose their sedentarism and become mobile. In high expression conditions of the PLAUR gene, a significant increase was seen in ZEB1, ZEB2 and SNAI2 gene activity that regulate the process of epithelial-mesenchymal transition. As a result of this, the glioma and neuroblastoma cells acquired increased mobility, typical for highly aggressive tumor subtypes inclined to the formation of multiple metastases.

"Our study showed that an artificial PLAUR gene amplification not only increases mobility of cancer cells, but comprehensively reprograms them, making the cells switch on the genes responsible for metastasis. This explains why patients with high levels of the uPAR protein (and, accordingly, with high PLAUR gene activity) in tumors often experience recurrence. That's why the uPAR protein may be seen as a promising target for new anticancer drugs. In the future, we are planning to study the impact of PLAUR gene knockout in order to get a fuller, more robust picture of its role in glioma and neuroblastoma tumor aggressiveness" — says Ekaterina Semina, doctor of biological sciences, head of the laboratory of translational research, professor at the department of public health and healthcare organization at the Higher School of Medicine at BFU named after Immanuel Kant.

More information:
doi.org/10.17650/2313-805X-2025-12-3-57-69

Provided by Immanuel Kant Baltic Federal University