Determining the Cause of Recurrence of Malignant Brain Tumor Glioblastoma...Reveal the neural stem cell mechanism
Mar 12, 2025
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Existing treatments have limitations in preventing recurrence, so they are known as brain tumors that are very difficult to treat.
Recently, a joint research team from Seoul National University Hospital, Yonsei Cancer Hospital, and the Korea Institute of Science and Technology has discovered that the source of glioblastoma recurrence may come from neural stem cells (NSCs) in the ventricular lower region. The results of this study, which identified the mechanism of glioblastoma recurrence and suggested the possibility of developing treatments targeting neural stem cells, were published in the latest issue of the international journal 'Molecular Cancer' (IF=27.7).
Most glioblastomas recur even if the tumor is removed as much as possible by surgery, and recurrence occurs mainly near the surgical site. Existing treatments such as surgery, radiation therapy, and chemotherapy have limitations in preventing this, so it was urgent to clarify the mechanism of recurrence of glioblastoma. The research team noted the possibility that neural stem cells play an important role in recurrence based on previous studies that have found that neural stem cells (cells with the ability to generate new neurons in the brain) in the ventricle are the source of tumor development.
The joint research team consisting of Professor Lee Ju-ho of the Department of Radiation Oncology at Seoul National University Hospital (first author Dr. Rishue), Professor Kang Seok-gu of Neurosurgery at Yonsei Cancer Hospital, and Professor Lee Jung-ho of the Korea Institute of Science and Technology said they experimentally proved the hypothesis that recurrence cancer can originate from distant neural stem cells, not just from residual cancer tissue, using genome analysis and mouse models.
The research team analyzed the genome system relationship between primary and recurrent cancers in 10 glioblastoma patients and found that recurrence cancer is genetically disconnected from primary cancer in 60% of patients, and instead, recurrence cancer is linked to ventricular sub-neural stem cells. These findings are important clues suggesting that neural stem cells may be the origin of recurrent cancer.
In addition, the research team conducted an experiment to track the origin of recurrence cancer using a double fluorescent mouse model. By labeling neural stem cells and tumor cells with other fluorescent proteins, it was possible to track the origin of the tumor. Through this, the research team identified the process by which neural stem cells move to the recurrence site after surgery to form a new tumor. This is an important result of proving that neural stem cells play an important role in the formation of recurrent cancer.
The team additionally found that the CXCR4/CXCL12 pathway induces the migration of neural stem cells and plays an important role in tumor reconstruction. The mechanism by which the CXCL12 signal molecule is secreted from vascular endothelial cells at the surgical resection site and binds to the CXCR4 receptor to attract neural stem cells to the surgical site and induce migration was identified through mouse experiments. The research team demonstrated that blocking this mechanism can reduce recurrence rates and improve survival rates by 60-70%. This finding suggests that treatments targeting CXCR4/CXCL12 may play an important role in preventing recurrence of glioblastoma.
Professor Lee Ju-ho (Radiation Oncology Department) at Seoul National University Hospital said "This study is significant in that it provides a new direction for glioblastoma treatment and research in the future by newly identifying the source of glioblastoma recurrence and discovering mechanisms that can block the interaction between the surgical site and neural stem cells.".
Meanwhile, this study was conducted with the support of the Korea Research Foundation and the Korea Health Industry Promotion Agency.
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This article was translated by Naver AI translator.
