Necrotic core in EMT6/Ro tumour spheroids: Is it caused by an ATP deficit?
Although commonly related to nutrient deprivation, the cause of the formation of the necrotic core in the multicellular tumour spheroids is still a controversial issue. We propose a simple model for the cell ATP production that assumes glucose and lactate as the only fuel substrates, and describes the main reactions occurring in the glycolytic and the oxidative pathways. Under the key assumption that cell death occurs when ATP production falls to a critical level, we formulate a multiscale model that integrates the energy metabolism at the cellular level with the diffusive transport of the metabolites in the spheroid mass. The model has been tested by predicting the measurements of the necrotic radius obtained by Freyer and Sutherland (1986a) in EMT6/Ro spheroids under different concentrations of glucose and oxygen in the culture medium. The results appear to be in agreement with the hypothesis that necrosis is caused by ATP deficit.
Bertuzzi
Alessandro
A
Istituto di Analisi dei Sistemi ed Informatica "A. Ruberti" - CNR, Roma, Italy. bertuzzi@iasi.cnr.it
Fasano
Antonio
A
Gandolfi
Alberto
A
Sinisgalli
Carmela
C
D000255:Adenosine Triphosphate / Q000172:deficiency* / Q000378:metabolism; D000818:Animals; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D005947:Glucose / Q000494:pharmacology; D019344:Lactic Acid / Q000378:metabolism / Q000494:pharmacology; D015674:Mammary Neoplasms, Animal / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008962:Models, Theoretical; D009336:Necrosis / Q000209:etiology / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D019344:Lactic Acid; D000255:Adenosine Triphosphate; D005947:Glucose; D010100:Oxygen