Untargeted metabolomics reveals distinct metabolic reprogramming in endothelial cells co-cultured with CSC and non-CSC prostate cancer cell subpopulations.
Untargeted metabolomics reveals distinct metabolic reprogramming in endothelial cells co-cultured with CSC and non-CSC prostate cancer cell subpopulations.
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DOI：
10.1371/journal.pone.0192175
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Cascante M
中科院分区：
文献类型：
--
作者：
Jayaraman A;Kumar P;Marin S;de Atauri P;Mateo F;M Thomson T;J Centelles J;F Graham S;Cascante M
肿瘤血管生成是癌症的一个重要标志，研究其代谢适应性，下游的任何细胞变化，可以揭示有吸引力的抑制癌症生长的目标。在肿瘤微环境中，内皮细胞（EC）与驱动血管生成和转移的异质肿瘤细胞类型相互作用。在这项研究中，我们的目的是表征的EC的代谢变化的影响下，存在的肿瘤细胞具有极端的转移能力。人脐静脉内皮细胞（HUVECs）进行不同的微环境条件下，如高转移性PC-3 M和高侵袭性PC-3S前列腺癌细胞系的存在下，除了血管生成激活剂血管内皮生长因子（VEGF），在常氧。基于代谢组学的非靶向高分辨率液相色谱-质谱（LC-MS）揭示了各种条件之间的显著代谢物差异，共鉴定了25种显著改变的代谢物，包括乙酰L-肉碱、NAD+、次黄嘌呤、鸟嘌呤和油酰胺，每种实验条件下的特征变化都是独特的。生化途径分析揭示了脂肪酸氧化和核苷酸补救途径的重要性。这些结果提供了一个全球性的代谢预览，可以帮助选择性地靶向EC，帮助癌细胞在异质性肿瘤微环境中侵袭或转移。
Tumour angiogenesis is an important hallmark of cancer and the study of its metabolic adaptations, downstream to any cellular change, can reveal attractive targets for inhibiting cancer growth. In the tumour microenvironment, endothelial cells (ECs) interact with heterogeneous tumour cell types that drive angiogenesis and metastasis. In this study we aim to characterize the metabolic alterations in ECs influenced by the presence of tumour cells with extreme metastatic abilities. Human umbilical vein endothelial cells (HUVECs) were subjected to different microenvironmental conditions, such as the presence of highly metastatic PC-3M and highly invasive PC-3S prostate cancer cell lines, in addition to the angiogenic activator vascular endothelial growth factor (VEGF), under normoxia. Untargeted high resolution liquid chromatography-mass spectrometry (LC-MS) based metabolomics revealed significant metabolite differences among the various conditions and a total of 25 significantly altered metabolites were identified including acetyl L-carnitine, NAD+, hypoxanthine, guanine and oleamide, with profile changes unique to each of the experimental conditions. Biochemical pathway analysis revealed the importance of fatty acid oxidation and nucleotide salvage pathways. These results provide a global metabolic preview that could help in selectively targeting the ECs aiding in either cancer cell invasion or metastasis in the heterogeneous tumour microenvironment.
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影响因子：
7.4
作者：
Dranka, Brian P.;Hill, Bradford G.;Darley-Usmar, Victor M.
通讯作者：
Darley-Usmar, Victor M.
影响因子：
7.4
作者：
Gowda, Harsha;Ivanisevic, Julijana;Johnson, Caroline H.;Kurczy, Michael E.;Benton, H. Paul;Rinehart, Duane;Thomas Nguyen;Ray, Jayashree;Kuehl, Jennifer;Arevalo, Bernardo;Westenskow, Peter D.;Wang, Junhua;Arkin, Adam P.;Deutschbauer, Adam M.;Patti, Gary J.;Siuzdak, Gary
通讯作者：
Siuzdak, Gary
影响因子：
64.5
作者：
De Bock, Katrien;Georgiadou, Maria;Carmeliet, Peter
通讯作者：
Carmeliet, Peter
影响因子：
21.3
作者：
通讯作者：
--
分子机制和血管生成的临床应用。
影响因子：
64.8
作者：
Carmeliet, Peter;Jain, Rakesh K.
通讯作者：
Jain, Rakesh K.