Schiffer Davide, Annovazzi Laura, Casalone Cristina, Corona Cristiano, Mellai Marta
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.
Cancers (Basel). 2018 Dec 20;11(1):5. doi: 10.3390/cancers11010005.
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.
生态位概念最初是为描述正常神经干细胞（NSCs）在脑室下区室管膜下层中的位置而提出的。在本文中，其意义已扩展至胶质母细胞瘤（GB）中肿瘤干细胞的定位，以探讨GB干细胞（GSCs）与内皮细胞（ECs）之间的关系。它们的相互作用基本上被认为是肿瘤生长、侵袭和复发的原因。生态位被描述为肿瘤微环境（TME）的最大表达点，因此包括肿瘤中除肿瘤细胞之外的所有成分：神经干细胞、反应性星形胶质细胞、内皮细胞、胶质瘤相关小胶质细胞/巨噬细胞（GAMs）、髓样细胞、周细胞、成纤维细胞等以及所有内在和外在信号通路。从病理学角度描述了血管周围（PVNs）、坏死周围（PNNs）和侵袭性生态位，突出了内皮细胞/肿瘤干细胞这一组合的基本重要性。基于GB的高增殖区域由GSCs/祖细胞组成这一概念，对PNN的发展进行了重新诠释。TME被描述为肿瘤中发生的一切的主要调节因子。特别强调了GAMs、周细胞和反应性星形胶质细胞是影响肿瘤细胞增殖、生长、侵袭和对治疗耐药性的重要因素。
