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Publication year
2006Author(s)
Source
Proceedings of the National Academy of Sciences USA, 103, 44, (2006), pp. 16466-71ISSN
Publication type
Article / Letter to editor

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Organization
Medical Microbiology
Radiation Oncology
Journal title
Proceedings of the National Academy of Sciences USA
Volume
vol. 103
Issue
iss. 44
Page start
p. 16466
Page end
p. 71
Subject
NCEBP 8: Psychological determinants of chronic illness; ONCOL 3: Translational research; UMCN 1.3: Tumor microenvironmentAbstract
In this work, highly infiltrative brain tumors with a stem-like phenotype were established by xenotransplantation of human brain tumors in immunodeficient nude rats. These tumors coopted the host vasculature and presented as an aggressive disease without signs of angiogenesis. The malignant cells expressed neural stem cell markers, showed a migratory behavior similar to normal human neural stem cells, and gave rise to tumors in vivo after regrafting. Serial passages in animals gradually transformed the tumors into an angiogenesis-dependent phenotype. This process was characterized by a reduction in stem cells markers. Gene expression profiling combined with high throughput immunoblotting analyses of the angiogenic and nonangiogenic tumors identified distinct signaling networks in the two phenotypes. Furthermore, proinvasive genes were up-regulated and angiogenesis signaling genes were down-regulated in the stem-like tumors. In contrast, proinvasive genes were down-regulated in the angiogenesis-dependent tumors derived from the stem-like tumors. The described angiogenesis-independent tumor growth and the uncoupling of invasion and angiogenesis, represented by the stem-like cancer cells and the cells derived from them, respectively, point at two completely independent mechanisms that drive tumor progression. This article underlines the need for developing therapies that specifically target the stem-like cell pools in tumors.
This item appears in the following Collection(s)
- Academic publications [227727]
- Electronic publications [107315]
- Faculty of Medical Sciences [86204]
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