Fidoamore Alessia, Cristiano Loredana, Antonosante Andrea, d'Angelo Michele, Di Giacomo Erica, Astarita Carlo, Giordano Antonio, Ippoliti Rodolfo, Benedetti Elisabetta, Cimini Annamaria
Department of Life, Health and Environmental Sciences, University of L'Aquila, 67100 L'Aquila, Italy.
Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA 19122, USA.
Stem Cells Int. 2016;2016:6809105. doi: 10.1155/2016/6809105. Epub 2016 Jan 6.
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.
在所有实体瘤中，高级别胶质瘤似乎是血管化程度最高的。事实上，“微血管增生”是胶质母细胞瘤（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到组织中氧气扩散距离之外，从而形成缺氧或无氧区域，胶质母细胞瘤干细胞（GSCs）大多位于这些区域。对此事件的反应是诱导血管生成，这是一个由缺氧诱导因子介导的过程。然而，这种新的毛细血管网络在为肿瘤块维持适当的氧气供应方面效率不高，从而在肿瘤区域内造成氧气梯度。这种微环境有助于GSCs保持“静止”状态，保留其增殖和分化的潜能，从而使其免受化疗和放疗的影响。最近的证据表明，胶质母细胞瘤对标准疗法的反应取决于GSCs所在的生态位微环境，通过保护GSCs，允许各种导致化疗和放疗抗性的机制。因此，研究生态位的组成部分/因素至关重要，以便制定新的辅助疗法，更有效地实施针对这种肿瘤的金标准疗法。
