Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Delineation of hypoxia-induced proteome shifts in osteosarcoma cells with different metastatic propensities.
Scientific Reports ( IF 3.8 ) Pub Date : 2020-01-20 , DOI: 10.1038/s41598-019-56878-x Zifeng Song 1 , Martin C Pearce 2 , Yuan Jiang 3 , Liping Yang 1 , Cheri Goodall 4 , Cristobal L Miranda 5 , Milan Milovancev 4 , Shay Bracha 4 , Siva K Kolluri 2, 5 , Claudia S Maier 1, 5
Scientific Reports ( IF 3.8 ) Pub Date : 2020-01-20 , DOI: 10.1038/s41598-019-56878-x Zifeng Song 1 , Martin C Pearce 2 , Yuan Jiang 3 , Liping Yang 1 , Cheri Goodall 4 , Cristobal L Miranda 5 , Milan Milovancev 4 , Shay Bracha 4 , Siva K Kolluri 2, 5 , Claudia S Maier 1, 5
Affiliation
|
Osteosarcoma (OS) is the most common bone cancer in children and young adults. Solid tumors are characterized by intratumoral hypoxia, and hypoxic cells are associated with the transformation to aggressive phenotype and metastasis. The proteome needed to support an aggressive osteosarcoma cell phenotype remains largely undefined. To link metastatic propensity to a hypoxia-induced proteotype, we compared the protein profiles of two isogenic canine OS cell lines, POS (low metastatic) and HMPOS (highly metastatic), under normoxia and hypoxia. Label-free shotgun proteomics was applied to comprehensively characterize the hypoxia-responsive proteome profiles in the OS cell phenotypes. Hypothesis-driven parallel reaction monitoring was used to validate the differential proteins observed in the shotgun data and to monitor proteins of which we expected to exhibit hypoxia responsiveness, but which were absent in the label-free shotgun data. We established a "distance" score (|zHMPOS - zPOS|), and "sensitivity" score (|zHypoxia - zNormoxia) to quantitatively evaluate the proteome shifts exhibited by OS cells in response to hypoxia. Evaluation of the sensitivity scores for the proteome shifts observed and principal component analysis of the hypoxia-responsive proteins indicated that both cell types acquire a proteome that supports a Warburg phenotype with enhanced cell migration and proliferation characteristics. Cell migration and glucose uptake assays combined with protein function inhibitor studies provided further support that hypoxia-driven adaption of pathways associated with glycolytic metabolism, collagen biosynthesis and remodeling, redox regulation and immunomodulatory proteins typify a proteotype associated with an aggressive cancer cell phenotype. Our findings further suggest that proteins involved in collagen remodeling and immune editing may warrant further evaluation as potential targets for anti-metastatic treatment strategies in osteosarcoma.
中文翻译：
具有不同转移倾向的骨肉瘤细胞中缺氧诱导的蛋白质组变化的描述。
骨肉瘤（OS）是儿童和年轻人中最常见的骨癌。实体瘤的特点是瘤内缺氧，缺氧细胞与侵袭性表型的转变和转移有关。支持侵袭性骨肉瘤细胞表型所需的蛋白质组在很大程度上仍不清楚。为了将转移倾向与缺氧诱导的蛋白质型联系起来，我们比较了两种同基因犬 OS 细胞系 POS（低转移性）和 HMPOS（高转移性）在常氧和缺氧下的蛋白质谱。应用无标记鸟枪蛋白质组学来全面表征 OS 细胞表型中的缺氧反应蛋白质组谱。假设驱动的平行反应监测用于验证在鸟枪数据中观察到的差异蛋白质，并监测我们预计其表现出缺氧反应性但在无标记鸟枪数据中不存在的蛋白质。我们建立了“距离”评分（|zHMPOS - zPOS|）和“敏感性”评分（|zHypoxia - zNormoxia）来定量评估 OS 细胞响应缺氧而表现出的蛋白质组变化。对观察到的蛋白质组变化的敏感性评分的评估和缺氧反应蛋白的主成分分析表明，两种细胞类型都获得了支持具有增强的细胞迁移和增殖特征的 Warburg 表型的蛋白质组。细胞迁移和葡萄糖摄取测定与蛋白质功能抑制剂研究相结合，进一步支持缺氧驱动的与糖酵解代谢、胶原生物合成和重塑、氧化还原调节和免疫调节蛋白相关途径的适应是与侵袭性癌细胞表型相关的典型蛋白质型。我们的研究结果进一步表明，参与胶原重塑和免疫编辑的蛋白质可能值得进一步评估，作为骨肉瘤抗转移治疗策略的潜在靶标。
更新日期：2020-01-21
中文翻译：
具有不同转移倾向的骨肉瘤细胞中缺氧诱导的蛋白质组变化的描述。
骨肉瘤（OS）是儿童和年轻人中最常见的骨癌。实体瘤的特点是瘤内缺氧，缺氧细胞与侵袭性表型的转变和转移有关。支持侵袭性骨肉瘤细胞表型所需的蛋白质组在很大程度上仍不清楚。为了将转移倾向与缺氧诱导的蛋白质型联系起来，我们比较了两种同基因犬 OS 细胞系 POS（低转移性）和 HMPOS（高转移性）在常氧和缺氧下的蛋白质谱。应用无标记鸟枪蛋白质组学来全面表征 OS 细胞表型中的缺氧反应蛋白质组谱。假设驱动的平行反应监测用于验证在鸟枪数据中观察到的差异蛋白质，并监测我们预计其表现出缺氧反应性但在无标记鸟枪数据中不存在的蛋白质。我们建立了“距离”评分（|zHMPOS - zPOS|）和“敏感性”评分（|zHypoxia - zNormoxia）来定量评估 OS 细胞响应缺氧而表现出的蛋白质组变化。对观察到的蛋白质组变化的敏感性评分的评估和缺氧反应蛋白的主成分分析表明，两种细胞类型都获得了支持具有增强的细胞迁移和增殖特征的 Warburg 表型的蛋白质组。细胞迁移和葡萄糖摄取测定与蛋白质功能抑制剂研究相结合，进一步支持缺氧驱动的与糖酵解代谢、胶原生物合成和重塑、氧化还原调节和免疫调节蛋白相关途径的适应是与侵袭性癌细胞表型相关的典型蛋白质型。我们的研究结果进一步表明，参与胶原重塑和免疫编辑的蛋白质可能值得进一步评估，作为骨肉瘤抗转移治疗策略的潜在靶标。
京公网安备 11010802027423号