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Identification of Metastasis-Associated Metabolic Profiles of Tumors by 1H-HR-MAS-MRS

机译:1H-HR-MAS-MRS鉴定肿瘤转移相关的代谢谱

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Tumors develop an abnormal microenvironment during growth, and similar to the metastatic phenotype, the metabolic phenotype of cancer cells is tightly linked to characteristics of the tumor microenvironment (TME). In this study, we explored relationships between metabolic profile, metastatic propensity, and hypoxia in experimental tumors in an attempt to identify metastasis-associated metabolic profiles. Two human melanoma xenograft lines (A-07, R-18) showing different TMEs were used as cancer models. Metabolic profile was assessed by proton high resolution magic angle spinning magnetic resonance spectroscopy (1H-HR-MAS-MRS). Tumor hypoxia was detected in immunostained histological preparations by using pimonidazole as a hypoxia marker. Twenty-four samples from 10 A-07 tumors and 28 samples from 10 R-18 tumors were analyzed. Metastasis was associated with hypoxia in both A-07 and R-18 tumors, and 1H-HR-MAS-MRS discriminated between tissue samples with and tissue samples without hypoxic regions in both models, primarily because hypoxia was associated with high lactate resonance peaks in A-07 tumors and with low lactate resonance peaks in R-18 tumors. Similarly, metastatic and non-metastatic R-18 tumors showed significantly different metabolic profiles, but not metastatic and non-metastatic A-07 tumors, probably because some samples from the metastatic A-07 tumors were derived from tumor regions without hypoxic tissue. This study suggests that 1H-HR-MAS-MRS may be a valuable tool for evaluating the role of hypoxia and lactate in tumor metastasis as well as for identification of metastasis-associated metabolic profiles.
机译:肿瘤在生长期间发育异常微环境,并且类似于转移表型,癌细胞的代谢表型与肿瘤微环境(TME)的特征紧密相关。在这项研究中,我们在实验肿瘤中探讨了代谢型材,转移性倾向和缺氧之间的关系,试图鉴定转移相关的代谢谱。显示出不同TME的两条人黑色素瘤异种移植物线(A-07,R-18)用作癌症模型。通过质子高分辨率魔角纺丝磁共振谱(1H-HR-MAS-MRS)评估代谢型材。通过使用吡喃唑作为缺氧标记,在免疫染色的组织学制剂中检测肿瘤缺氧。分析了来自10 A-07肿瘤的二十四个样品和来自10 r-18肿瘤的28个样品。转移与A-07和R-18肿瘤的缺氧相关,并且在两种模型中没有缺氧区域的组织样品之间的1H-HR-MAS-MRS,主要是因为缺氧与高乳酸共振峰有关A-07肿瘤和R-18肿瘤中的低乳酸共振峰。类似地,转移性和非转移性R-18肿瘤显示出显着不同的代谢谱,但不能转移和非转移A-07肿瘤,可能是因为来自转移A-07肿瘤的一些样品源自没有缺氧组织的肿瘤区域。本研究表明,1H-HR-MAS-MRS可以是评估缺氧和乳酸在肿瘤转移中的作用的有价值的工具,以及鉴定转移相关的代谢谱。

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