Analysis of angiogenesis related factors in glioblastoma, peritumoral tissue and their derived cancer stem cells.
Analysis of angiogenesis related factors in glioblastoma, peritumoral tissue and their derived cancer stem cells.
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DOI：
10.18632/oncotarget.12398
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发表时间：
2016-11-29
期刊：
影响因子：
--
通讯作者：
Sica G
中科院分区：
文献类型：
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作者：
D'Alessio A;Proietti G;Lama G;Biamonte F;Lauriola L;Moscato U;Vescovi A;Mangiola A;Angelucci C;Sica G
新血管的形成代表了生理和病理情况下的关键事件。在这项研究中，我们通过免疫组织化学，和/或蛋白质印迹和/或定量真实的时间PCR评估了HIF 1 α，HIF 2 α，VEGF，VEGFR 1和VEGFR 2在50例患者的手术多形性胶质母细胞瘤（GBM）和瘤周组织样本中的表达，以及从5例患者的GBM（GCSC）和瘤周组织（PCSC）分离的癌症干细胞（CSC）中的表达。我们还研究了GCSC和PCSC对体外内皮细胞（EC）行为的贡献。免疫组化显示GBM和瘤周组织中均表达血管生成标志物。此外，体外管形成实验表明，GCSC和PCSC都刺激EC增殖以及管状血管形成。主要观察到增加的迁移能力时，EC的存在下培养的GCSC，而不是在PCSC的存在下。这些结果表明，相关的新生血管发生事件可能发生在GBM。特别是，PCSC中VEGF/VEGFR共表达导致假设参与自分泌信号传导。此外，我们的结果表明GCSC和PCSC都拥有激活“血管生成开关”的技能和调节EC行为的能力，这表明这两种细胞类型要么对血管生成刺激有反应，要么能够触发血管生成反应。与我们以前的研究结果一起，这项研究进一步增加了一个具有挑战性的难题，即瘤周组织的特征及其在GBM病理生理学中真实的作用的定义。
The formation of new blood vessels represents a crucial event under both physiological and pathological circumstances. In this study, we evaluated by immunohistochemistry, and/or Western blotting and/or quantitative real time-PCR the expression of HIF1α, HIF2α, VEGF, VEGFR1 and VEGFR2 in surgical glioblastoma multiforme (GBM) and peritumoral tissue samples obtained from 50 patients as well as in cancer stem cells (CSCs) isolated from GBM (GCSCs) and peritumoral tissue (PCSCs) of 5 patients. We also investigated the contribution of both GCSCs and PCSCs on the behavior of endothelial cells (ECs) in vitro. Immunohistochemistry demonstrated the expression of angiogenesis markers in both GBM and peritumoral tissue. In addition, in vitro tube formation assay indicated that both GCSCs and PCSCs stimulate EC proliferation as well as tube-like vessel formation. An increased migration aptitude was mainly observed when ECs were cultured in the presence of GCSCs rather than in the presence of PCSCs. These findings suggest that relevant neoangiogenetic events may occur in GBM. In particular, VEGF/VEGFR co-expression in PCSCs leads to hypothesize the involvement of an autocrine signaling. Moreover, our results suggest that both GCSCs and PCSCs own the skill of activating the “angiogenic switch” and the capability of modulating EC behavior, indicating that both cell types are either responsive to angiogenic stimuli or able to trigger angiogenic response. Together with our previous findings, this study adds a further piece to the challenging puzzle of the characterization of peritumoral tissue and of the definition of its real role in GBM pathophysiology.