Institute of Cancer and Genomics Sciences, University of Birmingham, Birmingham, UK.
Research and Development, Qatar Research Leadership Program, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar.
Prog Neurobiol. 2018 Nov;170:37-52. doi: 10.1016/j.pneurobio.2018.04.007. Epub 2018 Apr 11.
The adult subventricular zone (SVZ) stem cell niche has proven vital for discovering neurodevelopmental mechanisms and holds great potential in medicine for neurodegenerative diseases. Yet the SVZ holds a dark side - it can become tumorigenic. Glioblastomas can arise from the SVZ via cancer stem cells (CSCs). Glioblastoma and other brain cancers often have dismal prognoses since they are resistant to treatment. In this review we argue that the SVZ is susceptible to cancer because it contains stem cells, migratory progenitors and unusual inflammation. Theoretically, SVZ stem cells can convert to CSCs more readily than can postmitotic neural cells. Additionally, the robust long-distance migration of SVZ progenitors can be subverted upon tumorigenesis to an infiltrative phenotype. There is evidence that the SVZ, even in health, exhibits chronic low-grade cellular and molecular inflammation. Its inflammatory response to brain injuries and disease differs from that of other brain regions. We hypothesize that the SVZ inflammatory environment can predispose cells to novel mutations and exacerbate cancer phenotypes. This can be studied in animal models in which human mutations related to cancer are knocked into the SVZ to induce tumorigenesis and the CSC immune interactions that precede full-blown cancer. Importantly inflammation can be pharmacologically modulated providing an avenue to brain cancer management and treatment. The SVZ is accessible by virtue of its location surrounding the lateral ventricles and CSCs in the SVZ can be targeted with a variety of pharmacotherapies. Thus, the SVZ can yield aggressive tumors but can be targeted via several strategies.
成人侧脑室下区（SVZ）干细胞巢对于发现神经发育机制至关重要，并且在神经退行性疾病的医学领域具有巨大的潜力。然而，SVZ 也有阴暗的一面——它可能具有致瘤性。神经胶质瘤可以通过癌症干细胞（CSC）从 SVZ 中产生。神经胶质瘤和其他脑癌通常预后不佳，因为它们对治疗有抵抗力。在这篇综述中，我们认为 SVZ 容易发生癌症，因为它包含干细胞、迁移祖细胞和异常炎症。从理论上讲，SVZ 干细胞比有丝分裂后神经细胞更容易转化为 CSC。此外，SVZ 祖细胞的强大长距离迁移在发生肿瘤时可以被逆转，表现为浸润表型。有证据表明，SVZ 即使在健康状态下，也表现出慢性低度细胞和分子炎症。它对脑损伤和疾病的炎症反应与其他脑区不同。我们假设 SVZ 的炎症环境可以使细胞容易发生新的突变，并加剧癌症表型。这可以在动物模型中进行研究，在这些模型中，与癌症相关的人类突变被敲入 SVZ 以诱导肿瘤发生和 CSC 免疫相互作用，从而导致癌症的全面发生。重要的是，炎症可以通过药理学调节来控制，为脑癌的管理和治疗提供了一种途径。SVZ 因其位于侧脑室周围的位置而易于接近，并且可以通过各种药物治疗来靶向 SVZ 中的 CSC。因此，SVZ 可以产生侵袭性肿瘤，但可以通过多种策略来靶向。
