Exosomal Proteome Profiling: A Potential Multi-Marker Cellular Phenotyping Tool to Characterize Hypoxia-Induced Radiation Resistance in Breast Cancer.
Exosomal Proteome Profiling: A Potential Multi-Marker Cellular Phenotyping Tool to Characterize Hypoxia-Induced Radiation Resistance in Breast Cancer.
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DOI：
10.3390/proteomes1020087
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发表时间：
2013-09-01
期刊：
影响因子：
3.3
通讯作者：
Yang AJ
中科院分区：
文献类型：
--
作者：
Thomas SN;Liao Z;Clark D;Chen Y;Samadani R;Mao L;Ann DK;Baulch JE;Shapiro P;Yang AJ
放射和耐药性是局部晚期、复发和转移性乳腺癌治疗中的重大挑战，这些癌症会导致死亡。临床上，放射治疗需要氧气来产生细胞毒性自由基，从而导致DNA损伤，并使这种损伤在基因组中得到修复，而不是修复。然而，大约40%的乳腺癌有低氧的肿瘤微环境，这使得癌细胞对辐射的抵抗力显著增强。低氧刺激引起细胞死亡/存活途径的改变，导致细胞对辐射的抵抗力增强。因此，评估乳腺癌肿瘤缺氧的非侵入性策略的发展最近受到了相当大的关注。Exosome是一种分泌的纳米囊泡，在乳腺肿瘤进展过程中发挥旁分泌信号作用，包括肿瘤-间质相互作用、增殖途径激活和免疫抑制。最近分离和纯化外切体的方案的发展，以及基于质谱学的蛋白质组学的进展，促进了对外切体内容和功能的全面分析。使用这些工具，研究已经证明，肿瘤来源的外切体的蛋白质组谱可以指示患者肿瘤的氧合状态。他们还证明，在肿瘤发生过程中，外切体信号通路是低氧依赖的细胞间信号的潜在靶向驱动因素。本文概述了蛋白质组学工具如何有效地用于表征外切体和阐明乳腺癌低氧介导的辐射耐药的基本信号通路和生存机制。
Radiation and drug resistance are significant challenges in the treatment of locally advanced, recurrent and metastatic breast cancer that contribute to mortality. Clinically, radiotherapy requires oxygen to generate cytotoxic free radicals that cause DNA damage and allow that damage to become fixed in the genome rather than repaired. However, approximately 40% of all breast cancers have hypoxic tumor microenvironments that render cancer cells significantly more resistant to irradiation. Hypoxic stimuli trigger changes in the cell death/survival pathway that lead to increased cellular radiation resistance. As a result, the development of noninvasive strategies to assess tumor hypoxia in breast cancer has recently received considerable attention. Exosomes are secreted nanovesicles that have roles in paracrine signaling during breast tumor progression, including tumor-stromal interactions, activation of proliferative pathways and immunosuppression. The recent development of protocols to isolate and purify exosomes, as well as advances in mass spectrometry-based proteomics have facilitated the comprehensive analysis of exosome content and function. Using these tools, studies have demonstrated that the proteome profiles of tumor-derived exosomes are indicative of the oxygenation status of patient tumors. They have also demonstrated that exosome signaling pathways are potentially targetable drivers of hypoxia-dependent intercellular signaling during tumorigenesis. This article provides an overview of how proteomic tools can be effectively used to characterize exosomes and elucidate fundamental signaling pathways and survival mechanisms underlying hypoxia-mediated radiation resistance in breast cancer.