Energy Metabolism Behavior and Response to Microenvironmental Factors of the Experimental Cancer Cell Models Differ from that of Actual Human Tumors
Por:
Moreno-Sánchez R., Vargas-Navarro J.L., Padilla-Flores J.A., Robledo-Cadena D.X., Granados-Rivas J.C., Taba R., Terasmaa A., Auditano G.L., Kaambre T., Rodriguez-Enriquez S.
Publicada:
1 ene 2025
Resumen:
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. © 2025 Bentham Science Publishers.
Filiaciones:
Moreno-Sánchez R.:
Laboratorio de Control Metabólico, Carrera de Biología, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Estado de México, Tlalnepantla de Baz, Mexico
Laboratory of Chemical Biology, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia
Vargas-Navarro J.L.:
Laboratorio de Control Metabólico, Carrera de Biología, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Estado de México, Tlalnepantla de Baz, Mexico
Padilla-Flores J.A.:
Laboratorio de Control Metabólico, Carrera de Biología, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Estado de México, Tlalnepantla de Baz, Mexico
Robledo-Cadena D.X.:
Departamento de Bioquímica, Instituto Nacional de Cardiología Ignacio Chávez, Juan Badiano No. 1. Colonia Sección XVI, Tlalpan, Mexico
Granados-Rivas J.C.:
Laboratorio de Control Metabólico, Carrera de Biología, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Estado de México, Tlalnepantla de Baz, Mexico
Taba R.:
Laboratory of Chemical Biology, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia
Terasmaa A.:
Laboratory of Chemical Biology, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia
Auditano G.L.:
Laboratory of Chemical Biology, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia
Kaambre T.:
Laboratory of Chemical Biology, National Institute of Chemical Physics and Biophysics, Tallinn, Estonia
Rodriguez-Enriquez S.:
Laboratorio de Control Metabólico, Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla de Baz, Estado de México, Mexico
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