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Open Access Highly Accessed Review

Molecular responses to hypoxia in tumor cells

Manfred Kunz1* and Saleh M Ibrahim2

Author Affiliations

1 University of Rostock, Department of Dermatology and Venereology, Augustenstr. 80–84, 18055 Rostock, Germany

2 University of Rostock, Institute of Immunology, Schillingallee 70, 18055 Rostock, Germany

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Molecular Cancer 2003, 2:23  doi:10.1186/1476-4598-2-23

Published: 17 April 2003

Abstract

Highly aggressive, rapidly growing tumors are exposed to hypoxia or even anoxia which occurs as a consequence of inadequate blood supply. Both hypoxia and consecutive hypoxia/reoxygenation exert a variety of influences on tumor cell biology. Among these are activation of certain signal transduction pathways and gene regulatory mechanisms, induction of selection processes for gene mutations, tumor cell apoptosis and tumor angiogenesis. Most of these mechanisms contribute to tumor progression. Therefore, tissue hypoxia has been regarded as a central factor for tumor aggressiveness and metastasis. In this review, we summarize the current knowledge about the molecular mechanisms induced by tumor cell hypoxia with a special emphasis on intracellular signal transduction, gene regulation, angiogenesis and apoptosis. Interfering with these pathways might open perspectives for future innovative treatment of highly aggressive metastasizing tumors.

Keywords:
Hypoxia; gene regulation; signal transduction; angiogenesis; apoptosis