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Glioblastoma: Microenvironment and Niche Concept

Professore Emerito di Neurologia, Università di Torino, Corso Bramante 88/90, 10126 Torino, Italy
Ex Centro Ricerche/Fondazione Policlinico di Monza, Via P. Micca 29, 13100 Vercelli, Italy
Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d’Aosta, Via Bologna 148, 10154 Torino, Italy
Dipartimento di Scienze della Salute, Scuola di Medicina, Università del Piemonte Orientale “A. Avogadro”, Corso Mazzini 18, 28100 Novara, Italy
Fondazione Edo ed Elvo Tempia Valenta—Onlus, Via Malta 3, 13900 Biella, Italy
Author to whom correspondence should be addressed.
Cancers 2019, 11(1), 5;
Received: 17 October 2018 / Revised: 7 December 2018 / Accepted: 7 December 2018 / Published: 20 December 2018
(This article belongs to the Special Issue Glioblastoma: State of the Art and Future Perspectives)
PDF [3426 KB, uploaded 20 December 2018]


The niche concept was originally developed to describe the location of normal neural stem cells (NSCs) in the subependymal layer of the sub-ventricular zone. In this paper, its significance has been extended to the location of tumor stem cells in glioblastoma (GB) to discuss the relationship between GB stem cells (GSCs) and endothelial cells (ECs). Their interaction is basically conceived as responsible for tumor growth, invasion and recurrence. Niches are described as the points of utmost expression of the tumor microenvironment (TME), therefore including everything in the tumor except for tumor cells: NSCs, reactive astrocytes, ECs, glioma-associated microglia/macrophages (GAMs), myeloid cells, pericytes, fibroblasts, etc. and all intrinsic and extrinsic signaling pathways. Perivascular (PVNs), perinecrotic (PNNs) and invasive niches were described from the pathological point of view, highlighting the basic significance of the EC/tumor stem cell couple. PNN development was reinterpreted based on the concept that hyperproliferative areas of GB are composed of GSCs/progenitors. TME was depicted in its function as the main regulator of everything that happens in the tumor. A particular emphasis was given to GAMs, pericytes and reactive astrocytes as important elements affecting proliferation, growth, invasion and resistance to therapies of tumor cells. View Full-Text
Keywords: glioblastoma; microenvironment; niche; pericytes; reactive astrocytes glioblastoma; microenvironment; niche; pericytes; reactive astrocytes

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Schiffer, D.; Annovazzi, L.; Casalone, C.; Corona, C.; Mellai, M. Glioblastoma: Microenvironment and Niche Concept. Cancers 2019, 11, 5.

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