Energy Metabolism Behavior and Response to Microenvironmental Factors of the Experimental Cancer Cell Models Differ From That of Actual Human Tumors.

IF 3.3 3区 医学 Q2 CHEMISTRY, MEDICINAL Mini reviews in medicinal chemistry Pub Date : 2024-10-15 DOI:10.2174/0113895575322436240924101642
Rafael Moreno-Sanchez, Jorge Luis Vargas-Navarro, Joaquín Alberto Padilla-Flores, Diana Xochiquetzal Robledo-Cadena, Juan Carlos Granados-Rivas, Rutt Taba, Anton Terasmaa, Giuseppe Leonardo Auditano, Tuuli Kaambre, Sara Rodríguez-Enríquez
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Abstract

Analysis of the biochemical differences in the energy metabolism among bi-dimensional (2D) and tri-dimensional (3D) cultured cancer cell models and actual human tumors was undertaken. In 2D cancer cells, the oxidative phosphorylation (OxPhos) fluxes range is 2.5-19 nmol O2/min/mg cellular protein. Hypoxia drastically decreased OxPhos flux by 2-3 times in 2D models, similar to what occurs in mature multicellular tumor spheroids (MCTS), a representative 3D cancer cell model. However, mitochondrial protein contents and enzyme activities were significantly different between both models. Moreover, glycolytic fluxes were also significantly different between 2D and MCTS. The glycolytic flux range in 2D models is 1-34 nmol lactate/min/mg cellular protein, whereas in MCTS the range of glycolysis fluxes is 60-80 nmol lactate/min/mg cellular. In addition, sensitivity to anticancer canonical and metabolic drugs was greater in MCTS than in 2D. Actual solid human tumor samples show lower (1.6-4.5 times) OxPhos fluxes compared to normoxic 2D cancer cell cultures. These observations indicate that tridimensional organization provides a unique microenvironment affecting tumor physiology, which has not been so far faithfully reproduced by the 2D environment. Thus, the analysis of the resemblances and differences among cancer cell models undertaken in the present study raises caution on the interpretation of results derived from 2D cultured cancer cells when they are extended to clinical settings. It also raises awareness about detecting which biological and environmental factors are missing in 2D and 3D cancer cell models to be able to reproduce the actual human tumor behavior.

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实验癌细胞模型的能量代谢行为和对微环境因素的反应与实际人类肿瘤不同
研究人员分析了二维(2D)和三维(3D)培养癌细胞模型与实际人类肿瘤在能量代谢方面的生化差异。在二维癌细胞中,氧化磷酸化(OxPhos)通量范围为 2.5-19 nmol O2/min/mg细胞蛋白。缺氧会使二维模型中的 OxPhos 通量急剧下降 2-3 倍,这与成熟的多细胞肿瘤球(MCTS)(一种代表性的三维癌细胞模型)中的情况相似。但是,两种模型的线粒体蛋白质含量和酶活性有显著差异。此外,2D 和 MCTS 的糖酵解通量也有显著差异。二维模型的糖酵解通量范围为 1-34 nmol lactate/min/mg细胞蛋白,而 MCTS 的糖酵解通量范围为 60-80 nmol lactate/min/mg细胞蛋白。此外,MCTS 对抗癌药物和代谢药物的敏感性也高于二维模型。与常氧二维癌细胞培养物相比,实际的实体人类肿瘤样本显示出更低的(1.6-4.5 倍)OxPhos 通量。这些观察结果表明,三维组织提供了影响肿瘤生理学的独特微环境,而二维环境迄今尚未忠实地再现这种微环境。因此,本研究对不同癌细胞模型之间的相似性和差异性进行了分析,提醒人们在解释从二维培养的癌细胞中得出的结果并将其推广到临床环境时要谨慎。它还提高了人们对检测二维和三维癌细胞模型中缺少哪些生物和环境因素以重现实际人类肿瘤行为的认识。
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来源期刊
CiteScore
7.80
自引率
0.00%
发文量
231
审稿时长
6 months
期刊介绍: The aim of Mini-Reviews in Medicinal Chemistry is to publish short reviews on the important recent developments in medicinal chemistry and allied disciplines. Mini-Reviews in Medicinal Chemistry covers all areas of medicinal chemistry including developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, drug targets, and natural product research and structure-activity relationship studies. Mini-Reviews in Medicinal Chemistry is an essential journal for every medicinal and pharmaceutical chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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