Irradiation induces glioblastoma cell senescence and senescence-associated secretory phenotype.

作者: Hee-Young Jeon , Jun-Kyum Kim , Seok Won Ham , Se-Yeong Oh , Jaebong Kim

DOI: 10.1007/S13277-015-4439-2

关键词: Cell cycleSurvival ratePhenotypeSenescenceBiologyChemotherapyCell growthRadiation therapyPathologyCell aging

摘要: Glioblastoma multiforme (GBM) is one of the most aggressive and fatal primary brain tumors in humans. The standard therapy for treatment GBM surgical resection, followed by radiotherapy and/or chemotherapy. However, frequency tumor recurrence patients very high, survival rate remains poor. Delineating mechanisms essential therapeutic advances. Here, we demonstrate that irradiation rendered 17-20 % cells dead, but resulted 60-80 % growth-arrested with increases senescence markers, such as senescence-associated beta-galactosidase-positive cells, H3K9me3-positive p53-p21(CIP1)-positive cells. Moreover, induced expression secretory phenotype (SASP) mRNAs NFκB transcriptional activity Strikingly, compared to injection non-irradiated into immune-deficient mice, co-injection irradiated faster growth histological features human GBM. Taken together, our findings suggest senescent SASP after likely main reasons post-radiotherapy patients.

参考文章(41)
Claudia Cerella, Cindy Grandjenette, Mario Dicato, Marc Diederich, Roles of Apoptosis and Cellular Senescence in Cancer and Aging Current Drug Targets. ,vol. 17, pp. 405- 415 ,(2016) , 10.2174/1389450116666150202155915
Bert Vogelstein, David Lane, Arnold J. Levine, Surfing the p53 network Nature. ,vol. 408, pp. 307- 310 ,(2000) , 10.1038/35042675
Igor B Roninson, Tumor Cell Senescence in Cancer Treatment Cancer Research. ,vol. 63, pp. 2705- 2715 ,(2003)
Bin-Zhi Qian, Jiufeng Li, Hui Zhang, Takanori Kitamura, Jinghang Zhang, Liam R. Campion, Elizabeth A. Kaiser, Linda A. Snyder, Jeffrey W. Pollard, CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis Nature. ,vol. 475, pp. 222- 225 ,(2011) , 10.1038/NATURE10138
Judith Campisi, Fabrizio d'Adda di Fagagna, Cellular senescence: when bad things happen to good cells Nature Reviews Molecular Cell Biology. ,vol. 8, pp. 729- 740 ,(2007) , 10.1038/NRM2233
H J Kim, N Hawke, A S Baldwin, NF-κB and IKK as therapeutic targets in cancer Cell Death & Differentiation. ,vol. 13, pp. 738- 747 ,(2006) , 10.1038/SJ.CDD.4401877
George P Atkinson, Susan E Nozell, Etty (Tika) N Benveniste, NF-kappaB and STAT3 signaling in glioma: targets for future therapies. Expert Review of Neurotherapeutics. ,vol. 10, pp. 575- 586 ,(2010) , 10.1586/ERN.10.21
Vincent Petit, Gérald Massonnet, Zofia Maciorowski, Jawida Touhami, Aurélie Thuleau, Fariba Némati, Julie Laval, Sophie Château-Joubert, Jean-Luc Servely, David Vallerand, Jean-Jacques Fontaine, Naomi Taylor, Jean-Luc Battini, Marc Sitbon, Didier Decaudin, Optimization of tumor xenograft dissociation for the profiling of cell surface markers and nutrient transporters. Laboratory Investigation. ,vol. 93, pp. 611- 621 ,(2013) , 10.1038/LABINVEST.2013.44
Isaac Yang, Manish K. Aghi, New advances that enable identification of glioblastoma recurrence Nature Reviews Clinical Oncology. ,vol. 6, pp. 648- 657 ,(2009) , 10.1038/NRCLINONC.2009.150