Stem cell niches in glioblastoma: a neuropathological view.
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.
Neuro-Bio-Oncology Center, Policlinico di Monza Foundation (Vercelli)/Consorzio di Neuroscienze, University of Pavia, Via Pietro Micca 29, 13100 Vercelli, Italy.
Davide
D
Schiffer
Neuro-Bio-Oncology Center, Policlinico di Monza Foundation (Vercelli)/Consorzio di Neuroscienze, University of Pavia, Via Pietro Micca 29, 13100 Vercelli, Italy.
Marta
0000-0002-9139-517X
M
Mellai
Neuro-Bio-Oncology Center, Policlinico di Monza Foundation (Vercelli)/Consorzio di Neuroscienze, University of Pavia, Via Pietro Micca 29, 13100 Vercelli, Italy.
Laura
0000-0002-8043-9886
L
Annovazzi
Neuro-Bio-Oncology Center, Policlinico di Monza Foundation (Vercelli)/Consorzio di Neuroscienze, University of Pavia, Via Pietro Micca 29, 13100 Vercelli, Italy.
Valentina
0000-0003-2148-2160
V
Caldera
Neuro-Bio-Oncology Center, Policlinico di Monza Foundation (Vercelli)/Consorzio di Neuroscienze, University of Pavia, Via Pietro Micca 29, 13100 Vercelli, Italy.
Angela
0000-0002-2226-8150
A
Piazzi
Neuro-Bio-Oncology Center, Policlinico di Monza Foundation (Vercelli)/Consorzio di Neuroscienze, University of Pavia, Via Pietro Micca 29, 13100 Vercelli, Italy ; Department of Neurosurgery, CTO Hospital, Via G. Zuretti 29, 10126 Turin, Italy.
Tetyana
T
Denysenko
Department of Neurosurgery, CTO Hospital, Via G. Zuretti 29, 10126 Turin, Italy.
Antonio
A
Melcarne
D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells; D009420:Nervous System / Q000473:pathology*; D055153:Stem Cell Niche
D009363:Neoplasm Proteins