The role of inflammation in subventricular zone cancer. (November 2018)

• Record Type: Journal Article
• Authors: Bardella, Chiara; Al-Shammari, Abeer R.; Soares, Luana; Tomlinson, Ian; O'Neill, Eric; Szele, Francis G.
• Is Part Of: Progress in neurobiology. Volume 170(2018)
• Page Start: 37
• Page End: 52
• Publication Date: 2018-11
• Subjects: ASPP2 apoptosis-stimulating protein of p53 with signature sequences of ankyrin repeat-, SH3 domain-, and proline-rich region-containing protein 2 -- CD complement of differentiation -- CNS central nervous system -- CP choroid plexus -- CSC cancer stem cell -- CSF cerebrospinal fluid -- EGF epidermal growth factor -- EGFr epidermal growth factor receptor -- EPO erythropoeitin -- FGF2 Fibroblast growth factor 2 -- GBM glioblastoma multiforme -- GFAP glial fibrillary acidic protein -- G-CSF granulocyte colony-stimulating factor -- HGF hepatocyte growth factor -- IDH1 isocitrate dehydrogenase 1 -- IFN-γ gamma interferon -- IGF-1 insulin growth factor-1 -- IL-10 interleukin 10 -- iPSC induced pluripotent stem cell -- NSC neural stem cell -- OCT4 octamer-binding transcription factor 4 -- PDGF platelet-derived growth factor -- PDGFr platelet-derived growth factor receptor -- RCAS replication competent avian-like sarcoma -- RMS rostral migratory stream -- ROS reactive oxygen species -- SCNT somatic cell nuclear transfer -- SDF-1 stromal cell derived factor-1 -- SHH sonic hedgehog -- SVZ subventricular zone -- TAP transit amplifying progenitor -- TMEV Thelier's murine encephalomyelitis virus -- TNFα tumor necrosis factor-alpha -- VEGF vascular endothelial growth factor; Subventricular zone -- Cancer stem cells -- Inflammation; Neurobiology -- Periodicals; Neurology -- Periodicals; Neurology -- Periodicals; Neurobiologie -- Périodiques; 612.8
• DOI: 10.1016/j.pneurobio.2018.04.007
• Languages: English
• ISSNs: 0301-0082

Abstract

Highlights: The SVZ is a unique inflammatory niche. Inflammation can induce mutations and cancer. Immune cells enter the brain through the SVZ. Pro-inflammatory Galectin-3 is expressed in and regulates the SVZ. The SVZ is a "growth factory". Brain cancers can arise from the SVZ. SVZ stem cells are a potential source of brain cancer. SVZ cells can modulate cancer stem cells. SVZ stem cells are regulated by inflammation. Inflammation and SVZ cancer can be targeted pharmacologically. Abstract: 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.