The role of inflammation in subventricular zone cancer

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.

The Role of SVZ Stem Cells in Glioblastoma

“…As discussed above, stem cells are scarce in the adult brain and can only grow in protective stem cells niches, including the hippocampus and the SVZ [31,32]. These NSCs already possess the ability to proliferate and thus they could transform more easily and rapidly into BTPCs than any other post-mitotic neural cell in the brain [99]. After certain variations, neural precursor cells could become BTPCs (Figure 2).…”

Classification of Progression Patterns in Glioblastoma: Analysis of Predictive Factors and Clinical Implications

“…To better address the clinical practice of patients with GBM, we should have a comprehensive understanding of predictive factors and prognostic potential of different progression patterns, especially for non-local failure. There is increasing evidence that the subventricular zone (SVZ) may be involved in the progression of GBM, because the dysregulated neural stem cells of SVZ can leave the niche and migrate over long distances, and finally contribute to the oncogenesis (11,12). Numerous studies have shown that patients whose lesions involved the SVZ have worse clinical outcomes and more aggressive patterns of recurrence (13,14).…”

LTBP1 plays a potential bridge between depressive disorder and glioblastoma

“…We found that those GBM patients with higher PHQ-9 and GAD-7 score have significantly worse prognosis than their lower scored counterparts. It seems the case that glioblastoma and depressive/anxiety disorder share some common etiological factors, such as inflammation [ 33 , 34 ], neurotransmitter metabolism [ 35 ], glutamine [ 36 , 37 ], neural plasticity [ 38 , 39 ], etc. Nevertheless, none of these factors were confirmed by further research.…”