A Spectroscopic Technique to Simultaneously Characterize Fatty Acid Uptake, Mitochondrial Activity, Vascularity, and Oxygen Saturation for Longitudinal Studies In Vivo.
A Spectroscopic Technique to Simultaneously Characterize Fatty Acid Uptake, Mitochondrial Activity, Vascularity, and Oxygen Saturation for Longitudinal Studies In Vivo.
复制标题
DOI：
10.3390/metabo12050369
复制
发表时间：
2022-04-19
期刊：
影响因子：
4.1
通讯作者：
中科院分区：
文献类型：
--
作者：
侵袭性乳腺癌已显示其代谢向增加的脂质催化剂转移，作为氧化磷酸化的主要碳源。在这项研究中，我们提出了一种技术，纵向监测脂质代谢和氧化磷酸化在临床前的肿瘤模型，研究代谢的变化与乳腺组织的发展和表征之间的代谢差异，原发性小鼠乳腺癌和正常乳腺组织。我们使用光学光谱来测量两种同时注射的外源性荧光代谢报告物的信号：TMRE（氧化磷酸化替代物）和Bodipy FL C16（脂质催化剂替代物）。我们利用逆蒙特卡罗算法来校正由组织光学特性引起的像差，并提取与氧化代谢相关的血管终点，特别是氧饱和度（SO2）和血红蛋白浓度（[Hb]）。我们广泛地验证了我们的光学方法，以证明我们的两个荧光代谢终点可以在没有化学或光学串扰的情况下进行测量，并且两个荧光团在体内的双重测量忠实地再现了每个荧光团独立的测量。然后，我们应用我们的方法来跟踪生长的4T1和67NR乳腺肿瘤和衰老的乳腺组织的代谢，所有这些组织类型都是高度代谢的组织类型。我们的研究结果表明，代谢的变化是乳腺年龄和肿瘤生长的函数，这些变化可以通过结合我们的系统测量的终点来最好地区分。将Bodipy FL C16和TMRE终点与SO2或[Hb]结合的聚类分析被证明是最有效的，可以最大限度地减少组内方差和最大限度地增加组间差异。我们的平台可以扩展到长期代谢灵活性对研究很重要的应用，例如肿瘤消退，休眠后复发和对癌症治疗的反应。
Aggressive breast cancer has been shown to shift its metabolism towards increased lipid catabolism as the primary carbon source for oxidative phosphorylation. In this study, we present a technique to longitudinally monitor lipid metabolism and oxidative phosphorylation in pre-clinical tumor models to investigate the metabolic changes with mammary tissue development and characterize metabolic differences between primary murine breast cancer and normal mammary tissue. We used optical spectroscopy to measure the signal of two simultaneously injected exogenous fluorescent metabolic reporters: TMRE (oxidative phosphorylation surrogate) and Bodipy FL C16 (lipid catabolism surrogate). We leverage an inverse Monte Carlo algorithm to correct for aberrations resulting from tissue optical properties and to extract vascular endpoints relevant to oxidative metabolism, specifically oxygen saturation (SO2) and hemoglobin concentration ([Hb]). We extensively validated our optical method to demonstrate that our two fluorescent metabolic endpoints can be measured without chemical or optical crosstalk and that dual measurements of both fluorophores in vivo faithfully recapitulate the measurements of each fluorophore independently. We then applied our method to track the metabolism of growing 4T1 and 67NR breast tumors and aging mammary tissue, all highly metabolic tissue types. Our results show the changes in metabolism as a function of mammary age and tumor growth, and these changes can be best distinguished through the combination of endpoints measured with our system. Clustering analysis incorporating both Bodipy FL C16 and TMRE endpoints combined with either SO2 or [Hb] proved to be the most effective in minimizing intra-group variance and maximizing inter-group differences. Our platform can be extended to applications in which long-term metabolic flexibility is important to study, for example in tumor regression, recurrence following dormancy, and responses to cancer treatment.
登录
查看更多内容
DOI：
10.1016/j.neo.2015.08.005
发表时间：
2015-08
期刊：
Neoplasia (New York, N.Y.)
影响因子：
--
作者：
Simões RV;Serganova IS;Kruchevsky N;Leftin A;Shestov AA;Thaler HT;Sukenick G;Locasale JW;Blasberg RG;Koutcher JA;Ackerstaff E
通讯作者：
Ackerstaff E
影响因子：
2.5
作者：
Richert, MM;Schwertfeger, KL;Anderson, SM
通讯作者：
Anderson, SM
影响因子：
3.5
作者：
Palmer, Gregory M.;Ramanujam, Nirmala
通讯作者：
Ramanujam, Nirmala
影响因子：
13.6
作者：
Liu Z;Pouli D;Alonzo CA;Varone A;Karaliota S;Quinn KP;Münger K;Karalis KP;Georgakoudi I
通讯作者：
Georgakoudi I
影响因子：
5.2
作者：
Pranzini E;Raugei G;Taddei ML
通讯作者：
Taddei ML