Glioblastoma Stem Cells Microenvironment: The Paracrine Roles of the Niche in Drug and Radioresistance.
Glioblastoma Stem Cells Microenvironment: The Paracrine Roles of the Niche in Drug and Radioresistance.
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DOI：
10.1155/2016/6809105
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发表时间：
2016
影响因子：
4.3
通讯作者：
Cimini A
中科院分区：
文献类型：
--
作者：
Fidoamore A;Cristiano L;Antonosante A;d'Angelo M;Di Giacomo E;Astarita C;Giordano A;Ippoliti R;Benedetti E;Cimini A
在所有实体瘤中，高级别胶质瘤似乎是血管化最多的一种。事实上，“微血管增生”是GBM的一个标志。改变的血管网络决定了不规则的血流，使得肿瘤细胞迅速扩散超出组织中氧气的扩散距离，从而形成低氧或缺氧区域，其中大部分胶质母细胞瘤干细胞（GSC）驻留。对该事件的反应是诱导血管生成，这是由缺氧诱导因子介导的过程。然而，这种新的毛细血管网络不能有效地维持对肿瘤块的适当氧气供应，从而导致肿瘤区内的氧气梯度。这种微环境有助于GSC保持“静止”状态，保持其增殖和分化的潜力，从而通过化疗和放疗的影响保护它们。最近的证据表明，胶质母细胞瘤对标准疗法的反应是由GSC所在的小生境的微环境决定的，通过保留GSC，允许各种有助于化疗和放射抗性的机制。因此，至关重要的是要调查的组成部分/因素的利基，以制定新的辅助治疗，使更有效的金标准治疗这种肿瘤。
Among all solid tumors, the high-grade glioma appears to be the most vascularized one. In fact, “microvascular hyperplasia” is a hallmark of GBM. An altered vascular network determines irregular blood flow, so that tumor cells spread rapidly beyond the diffusion distance of oxygen in the tissue, with the consequent formation of hypoxic or anoxic areas, where the bulk of glioblastoma stem cells (GSCs) reside. The response to this event is the induction of angiogenesis, a process mediated by hypoxia inducible factors. However, this new capillary network is not efficient in maintaining a proper oxygen supply to the tumor mass, thereby causing an oxygen gradient within the neoplastic zone. This microenvironment helps GSCs to remain in a “quiescent” state preserving their potential to proliferate and differentiate, thus protecting them by the effects of chemo- and radiotherapy. Recent evidences suggest that responses of glioblastoma to standard therapies are determined by the microenvironment of the niche, where the GSCs reside, allowing a variety of mechanisms that contribute to the chemo- and radioresistance, by preserving GSCs. It is, therefore, crucial to investigate the components/factors of the niche in order to formulate new adjuvant therapies rendering more efficiently the gold standard therapies for this neoplasm.