Chemoresistance acquisition induces a global shift of expression of aniogenesis-associated genes and increased pro-angogenic activity in neuroblastoma cells

Michaelis, M., Klassert, D., Barth, S., Suhan, T., Breitling, R. , Mayer, B., Hinsch, N., Doerr, H. and Cinatl, J. (2009) Chemoresistance acquisition induces a global shift of expression of aniogenesis-associated genes and increased pro-angogenic activity in neuroblastoma cells. Molecular Cancer, 8(80), (doi: 10.1186/1476-4598-8-80)

Abstract

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 mechanims 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Breitling, Professor Rainer
• Authors: Michaelis, M., Klassert, D., Barth, S., Suhan, T., Breitling, R., Mayer, B., Hinsch, N., Doerr, H., and Cinatl, J.
• Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer); Q Science > QH Natural history > QH301 Biology
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Molecular Cancer
• Publisher: BioMed Central
• ISSN (Online): 1476-4598
• Published Online: 29 September 2009
• Copyright Holders: Copyright © 2009 The Authors
• First Published: First published in Molecular Cancer 8(80)
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher