Necrotic core in EMT6/Ro tumour spheroids: Is it caused by an ATP deficit?

JOURNAL OF THEORETICAL BIOLOGY

卷:262

Article

Bertuzzi, Alessandro¹  Fasano, Antonio²  Gandolfi, Alberto¹  Sinisgalli, Carmela¹ 

[1] CNR, Ist Anal Sistemi & Informat A Ruberti, I-00185 Rome, Italy

[2] Univ Florence, Dipartimento Matemat U Dini, I-50134 Florence, Italy

关键词: Tumour spheroid;    Necrosis;    Energy metabolism;    ATP;    Diffusive transport;    Free boundary problems;   

DOI  :  10.1016/j.jtbi.2009.09.024

来源: Elsevier

【 摘 要 】

Although commonly related to nutrient deprivation, the cause of the formation of the necrotic core in the multicellular turnout 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. (C) 2009 Elsevier Ltd. All rights reserved.

【 授权许可】

Free