Chemoresistance acquisition induces a global shift of expression of aniogenesis-associated genes and increased pro-angogenic activity in neuroblastoma cells.
| Autor: | Michaelis M; Institut für Medizinische Virologie, Klinikum der J,W, Goethe-Universität, Paul Ehrlich-Str, 40, 60596 Frankfurt am Main, Germany. michaelis@em.uni-frankfurt.de, Klassert D, Barth S, Suhan T, Breitling R, Mayer B, Hinsch N, Doerr HW, Cinatl J, Cinatl J Jr |
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| Jazyk: | angličtina |
| Zdroj: | Molecular cancer [Mol Cancer] 2009 Sep 29; Vol. 8, pp. 80. Date of Electronic Publication: 2009 Sep 29. |
| DOI: | 10.1186/1476-4598-8-80 |
| Abstrakt: | Background: Chemoresistance acquisition may influence cancer cell biology. Here, bioinformatics analysis of gene expression data was used to identify chemoresistance-associated changes in neuroblastoma biology. Results: Bioinformatics analysis of gene expression data revealed that expression of angiogenesis-associated genes significantly differs between chemosensitive and chemoresistant neuroblastoma cells. A subsequent systematic analysis of a panel of 14 chemosensitive and chemoresistant neuroblastoma cell lines in vitro and in animal experiments indicated a consistent shift to a more pro-angiogenic phenotype in chemoresistant neuroblastoma cells. The molecular mechanisms underlying increased pro-angiogenic activity of neuroblastoma cells are individual and differ between the investigated chemoresistant cell lines. Treatment of animals carrying doxorubicin-resistant neuroblastoma xenografts with doxorubicin, a cytotoxic drug known to exert anti-angiogenic activity, resulted in decreased tumour vessel formation and growth indicating chemoresistance-associated enhanced pro-angiogenic activity to be relevant for tumour progression and to represent a potential therapeutic target. Conclusion: A bioinformatics approach allowed to identify a relevant chemoresistance-associated shift in neuroblastoma cell biology. The chemoresistance-associated enhanced pro-angiogenic activity observed in neuroblastoma cells is relevant for tumour progression and represents a potential therapeutic target. |
| Databáze: | MEDLINE |
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