期刊
JOURNAL OF THEORETICAL BIOLOGY
卷 272, 期 1, 页码 55-63出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jtbi.2010.12.010
关键词
Stochastic model; Cancer; Hypoxia; Angiogenesis
资金
- Associazione Genitori contro le Leucemie e Tumori Infantili Noi per Voi
- Associazione Italiana per la Ricerca sul Cancro
- Istituto Toscano Tumori
- Ente Cassa di Risparmio di Firenze to the Dipartimento di Patologia e Oncologia Sperimentali
- Universita degli Studi di Firenze
A model is proposed to study the process of hypoxia-induced angiogenesis in cancer cells. The model accounts for the role played by the vascular endothelial growth factor (VEGF)-A in regulating the oxygen intake. VEGF-A is dynamically controlled by the HIF-1 beta concentration. If not degraded, HIF-1 alpha can bind to the subunit termed HIF-1 beta and so experience translocation to the nucleus, to exert its proper transcriptional activity. The delicate balance between these opposing tendencies translates into the emergence of distinct macroscopic behaviors in terms of the associated molecular concentrations that we here trace back to normoxia, hypoxia and death regimes. These aspects are firstly analyzed with reference to the ideal mean-field scenario. Stochastic fluctuations are also briefly discussed and shown to seed a cooperative interaction among cellular units, competing for the same oxygen reservoir. (c) 2010 Elsevier Ltd. All rights reserved.
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