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New trends in cancer for the 21st centuryEffect of Hypoxia on the Tumor Phenotype: The Neuroblastoma and Breast Cancer Models

New trends in cancer for the 21st century: Effect of Hypoxia on the Tumor Phenotype: The... CHAPTER 16 EFFECT OF HYPOXIA ON THE TUMOR PHENOTYPE: THE NEUROBLASTOMA AND BREAST CANCER MODELS LINDA HOLMQUIST, TOBIAS LÖFSTEDT, AND SVEN PÅHLMAN Department of Laboratory Medicine, Molecular Medicine, Lund University, University Hospital MAS, Malmö, Sweden Abstract: The tumor oxygenation status associates with aggressive behavior. Oxygen shortage, hypoxia, is a major driving force behind tumor vascularization, and hypoxia enhances mutational rate, metastatic spread, and resistance to radiation and chemotherapy. We recently discovered that hypoxia promotes dedifferentiation of neuroblastoma and breast carcinoma cells and development of stem cell-like features. In both these tumor forms there is a correlation between low differentiation stage and poor outcome, and we conclude that the dedifferentiating effect of lowered oxygen adds to the aggressive phenotype induced by hypoxia. With neuroblastoma and breast carcinoma as human tumor model systems, we have addressed questions related to hypoxia-induced molecular mechanisms governing malignant behavior of tumor cells, with emphasis on differentiation and growth control. By global gene expression analyses we are currently screening for gene products exclusively expressed or modified in hypoxic cells with the aim to use them as targets for treatment. 1. INTRODUCTION Cancer is a multigenetic disease, and the tumor origin determines, at least in part, which http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png

New trends in cancer for the 21st centuryEffect of Hypoxia on the Tumor Phenotype: The Neuroblastoma and Breast Cancer Models

Part of the Advances in Experimental Medicine and Biology Book Series (volume 587)
Editors: Llombart-Bosch, Antonio; Felipo, Vicente; López-Guerrero, José Antonio

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References (10)

Publisher
Springer Netherlands
Copyright
© Springer Science+Business Media B.V. 2006
ISBN
978-1-4020-4966-8
Pages
179 –193
DOI
10.1007/978-1-4020-5133-3_16
Publisher site
See Chapter on Publisher Site

Abstract

CHAPTER 16 EFFECT OF HYPOXIA ON THE TUMOR PHENOTYPE: THE NEUROBLASTOMA AND BREAST CANCER MODELS LINDA HOLMQUIST, TOBIAS LÖFSTEDT, AND SVEN PÅHLMAN Department of Laboratory Medicine, Molecular Medicine, Lund University, University Hospital MAS, Malmö, Sweden Abstract: The tumor oxygenation status associates with aggressive behavior. Oxygen shortage, hypoxia, is a major driving force behind tumor vascularization, and hypoxia enhances mutational rate, metastatic spread, and resistance to radiation and chemotherapy. We recently discovered that hypoxia promotes dedifferentiation of neuroblastoma and breast carcinoma cells and development of stem cell-like features. In both these tumor forms there is a correlation between low differentiation stage and poor outcome, and we conclude that the dedifferentiating effect of lowered oxygen adds to the aggressive phenotype induced by hypoxia. With neuroblastoma and breast carcinoma as human tumor model systems, we have addressed questions related to hypoxia-induced molecular mechanisms governing malignant behavior of tumor cells, with emphasis on differentiation and growth control. By global gene expression analyses we are currently screening for gene products exclusively expressed or modified in hypoxic cells with the aim to use them as targets for treatment. 1. INTRODUCTION Cancer is a multigenetic disease, and the tumor origin determines, at least in part, which

Published: Jan 1, 2006

Keywords: Neuroblastoma Cell; Human Neuroblastoma Cell; Hypoxic Cell; Tumor Phenotype; Prolyl Hydroxylase

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