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Stem cell niches in glioblastoma: a neuropathological view
Davide Schiffer1, Marta Mellai1, Laura Annovazzi1
1Neuro-Bio-Oncology Center, Policlinico di Monza Foundation (Vercelli)/Consorzio di Neuroscienze, University of Pavia, Via Pietro Micca 29, 13100 Vercelli, Italy.
Abstract:
Glioblastoma (GBM) stem cells (GSCs), responsible for tumor growth, recurrence, and resistance to therapies, are considered the real therapeutic target, if they had no molecular mechanisms of resistance, in comparison with the mass of more differentiated cells which are insensitive to therapies just because of being differentiated and nonproliferating. GSCs occur in tumor niches where both stemness status and angiogenesis are conditioned by the microenvironment. In both perivascular and perinecrotic niches, hypoxia plays a fundamental role. Fifteen glioblastomas have been studied by immunohistochemistry and immunofluorescence for stemness and differentiation antigens. It has been found that circumscribed necroses develop inside hyperproliferating areas that are characterized by high expression of stemness antigens. Necrosis developed inside them because of the imbalance between the proliferation of tumor cells and endothelial cells; it reduces the number of GSCs to a thin ring around the former hyperproliferating area. The perinecrotic GSCs are nothing else that the survivors remnants of those populating hyperproliferating areas. In the tumor, GSCs coincide with malignant areas so that the need to detect where they are located is not so urgent.
Insights
Glioblastoma stem cells (GSCs) drive tumor growth and resistance. Hypoxia in tumor niches influences GSCs, with necrosis forming in hyperproliferating areas, leaving GSCs as survivors in a ring around these zones.
Area of Science:
- Neuro-oncology
- Cancer stem cell biology
- Tumor microenvironment research
Background:
- Glioblastoma stem cells (GSCs) are key drivers of tumor growth, recurrence, and therapeutic resistance.
- GSCs reside in specific tumor niches (perivascular, perinecrotic) where microenvironmental factors like hypoxia influence their behavior and angiogenesis.
- Understanding GSC localization and resistance mechanisms is crucial for developing effective glioblastoma treatments.
Purpose of the Study:
- To investigate the relationship between glioblastoma stem cell distribution, necrosis, and hyperproliferation.
- To elucidate the role of the tumor microenvironment, particularly hypoxia, in shaping GSC populations.
- To identify the spatial characteristics of GSCs within glioblastoma tumors.
Main Methods:
- Immunohistochemistry and immunofluorescence staining of fifteen glioblastoma samples.
- Analysis of stemness and differentiation antigens to identify GSC populations.
- Microscopic examination to correlate GSC distribution with areas of necrosis and proliferation.
Main Results:
- Circumscribed necroses were observed within hyperproliferating areas characterized by high stemness antigen expression.
- Tumor cell and endothelial cell proliferation imbalance leads to necrosis, reducing GSC numbers to a ring around these necrotic zones.
- Perinecrotic GSCs represent surviving populations from previously hyperproliferating areas.
Conclusions:
- Glioblastoma stem cells are spatially associated with malignant areas within the tumor.
- The formation of necrosis influences GSC distribution, concentrating survivors around necrotic cores.
- Identifying GSC locations within the broader malignant areas may not be urgently required due to their co-localization.
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