Profiling Anti-Apoptotic BCL-xL Protein Expression in Glioblastoma Tumorspheres.
Profiling Anti-Apoptotic BCL-xL Protein Expression in Glioblastoma Tumorspheres.
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分析胶质母细胞瘤肿瘤球中的抗凋亡BCL-xL蛋白表达。
DOI：
10.3390/cancers12102853
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发表时间：
2020-10-02
期刊：
影响因子：
5.2
通讯作者：
Ichim G
中科院分区：
文献类型：
--
作者：
Fanfone D;Idbaih A;Mammi J;Gabut M;Ichim G
胶质母细胞瘤是一种生长迅速且侵袭性极强的脑肿瘤。它的治疗通常基于放射和化疗，由于胶质母细胞瘤干细胞，这些治疗是无效的。事实上，这些细胞通常对治疗有抵抗力，并且是肿瘤再生长的来源。因此，了解胶质母细胞瘤干细胞的存活是如何调节的可能会带来新的治疗机会。我们在这里表明，某些胶质母细胞瘤细胞，在特定条件下生长，有利于胶质母细胞瘤干细胞增殖，具有更高的BCL-xL表达，这是一种防止癌细胞死亡的蛋白质。这种对BCL-xL的依赖性可以用特定的BH 3模拟物药物进行治疗靶向，这些药物被设计用于抑制BCL-xL，从而诱导有效的胶质母细胞瘤细胞死亡。总的来说，我们的研究主张更好地了解如何特异性靶向BCL-xL以触发胶质母细胞瘤细胞死亡。胶质母细胞瘤（GBM）是预后最差的癌症之一，尽管人们付出了巨大的努力来了解其不寻常的异质性和侵袭性。这主要是由于胶质母细胞瘤干细胞（GSC），这也是手术，化疗或放疗后频繁肿瘤复发的原因。在这项研究中，我们研究了抗凋亡BCL-xL蛋白在几种GBM细胞系中的表达模式，以及它在富含GSC的肿瘤球中可能发挥的作用。我们报告说，几个GBM细胞系有一个增加的BCL-xL表达的肿瘤球相比，分化的细胞。此外，通过人工调节BCL-xL表达，我们解开了BCL-xL和肿瘤球大小之间的相关性。此外，BCL-xL上调似乎使GBM肿瘤球对新开发的BH 3模拟物敏感，为治疗GBM患者开辟了有希望的治疗前景。
Glioblastoma is a fast-growing and very aggressive brain tumor. Its treatment is usually based on radiation and chemotherapy, which are inefficient owing to glioblastoma stem cells. Indeed, these cells are often resistant to therapy and are a source of tumor regrowth. Therefore, understanding how the survival of glioblastoma stem cells is regulated might unlock new therapeutic opportunities. We show here that certain glioblastoma cells, grown in specific conditions to favor glioblastoma stem cell proliferation, have a higher expression of BCL-xL, a protein preventing cancer cell death. This dependency on BCL-xL can be therapeutically targeted with specific BH3 mimetics drugs, designed to inhibit BCL-xL and thus induce efficient glioblastoma cell death. Overall, our study advocates for a better understanding of how to specifically target BCL-xL to trigger glioblastoma cell death. Glioblastoma (GBM) is one of the cancers with the worst prognosis, despite huge efforts to understand its unusual heterogeneity and aggressiveness. This is mainly due to glioblastoma stem cells (GSCs), which are also responsible for the frequent tumor recurrence following surgery, chemotherapy or radiotherapy. In this study, we investigate the expression pattern of the anti-apoptotic BCL-xL protein in several GBM cell lines and the role it might play in GSC-enriched tumorspheres. We report that several GBM cell lines have an increased BCL-xL expression in tumorspheres compared to differentiated cells. Moreover, by artificially modulating BCL-xL expression, we unravel a correlation between BCL-xL and tumorsphere size. In addition, BCL-xL upregulation appears to sensitize GBM tumorspheres to newly developed BH3 mimetics, opening promising therapeutic perspectives for treating GBM patients.
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