Species-Specific Quantitative Proteomics Profiles of Sarcoma Patient-Derived Models Closely Reflect Their Primary Tumors.
Species-Specific Quantitative Proteomics Profiles of Sarcoma Patient-Derived Models Closely Reflect Their Primary Tumors.
复制标题
肉瘤患者衍生模型的物种特异性定量蛋白质组学特征密切反映了其原发肿瘤。
DOI：
10.1002/prca.201900054
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Kondo T.
中科院分区：
文献类型：
--
作者：
Shiozawa K;Oyama R;Takahashi M;Kito F;Hattori E;Yoshida A;Kawai A;Ono M;Kondo T.
PurposeThe purpose is to examine whether patient‐derived sarcoma models recapitulate the spectrum of sarcoma heterogeneity seen in patients.Experimental designTo characterize patient‐derived models for functional studies，proteomic comparison with originating sarcoma representative of three intrinsic subtypes by MS are performed.ResultsHuman protein profiling was found to be retained with high fidelity in patient‐derived models.通过种属特异性定量蛋白质组学表征患者肉瘤肿瘤和小鼠间质的蛋白质谱。小鼠间质中的蛋白质表达水平受到原发性人类肿瘤的影响。来源于肿瘤的基质蛋白在PDXs和细胞系中的水平较低，并且一些人基质蛋白在PDXs.Conclusions和临床意义中被相应的小鼠蛋白所取代，这些发现表明微环境对药物反应的影响可能不反映原发肿瘤中的那些。PDX中的这种跨物种蛋白质组学分析可以潜在地改善治疗方式的临床前评估，并提高预测临床试验反应的能力。
PurposeThe purpose is to examine whether patient‐derived sarcoma models recapitulate the spectrum of sarcoma heterogeneity seen in patients.Experimental designTo characterize patient‐derived models for functional studies, proteomic comparisons with originating sarcomas representative of three intrinsic subtypes by MS are performed.ResultsHuman protein profiling is found to be retained with high fidelity in patient‐derived models. The protein profiles of patient sarcoma tumors and mouse stroma are characterized by species‐specific quantitative proteomics. Protein‐expression levels in mouse stroma are affected by the primary human tumor. The levels of stromal proteins derived from tumors are lower in PDXs and cell lines, and some human stromal proteins are replaced by the corresponding mouse proteins in PDXs.Conclusions and clinical relevanceThese findings suggest that the effects of the microenvironment on drug responses may not reflect those in the primary tumor. This cross‐species proteomic analysis in PDXs can potentially improve preclinical evaluation of treatment modalities and enhance the ability to predict clinical trial responses.