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PMID: 17056721 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Angiogenesis-independent tumor growth mediated by stem-like cancer cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 103 ·No. 44 ·2006-10-31 ·Pages 16466-71

Sakariassen PØ, Prestegarden L, Wang J, Skaftnesmo KO, Mahesparan R, Molthoff C, Sminia P, Sundlisaeter E, Misra A, Tysnes BB, Chekenya M, Peters H, Lende G, Kalland KH, Øyan AM, Petersen K, Jonassen I, van der Kogel A, Feuerstein BG, Terzis AJ, Bjerkvig R, Enger PØ

Abstract

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.

MeSH Terms
Animals Biopsy Chromosomes, Human/genetics Disease Progression Gene Expression Regulation Humans Immunohistochemistry Neoplasm Invasiveness Neoplasm Transplantation Neoplasms/blood supply,genetics,pathology Phenotype Rats Rats, Nude Signal Transduction Stem Cells Survival Rate Tumor Cells, Cultured
Authors & Affiliations
22 authors, click to expand affiliations / ORCID
Sakariassen Per Ø
NorLux NeuroOncology, Department of Biomedicine, University of Bergen, N-5020 Bergen, Norway.
Prestegarden Lars
Wang Jian
Skaftnesmo Kai-Ove
Mahesparan Rupavathana
Molthoff Carla
Sminia Peter
Sundlisaeter Eirik
Misra Anjan
Tysnes Berit Bølge
Chekenya Martha
Peters Hans
Lende Gabriel
Kalland Karl Henning
Øyan Anne M
Petersen Kjell
Jonassen Inge
van der Kogel Albert
Feuerstein Burt G
Terzis A Jorge A
Bjerkvig Rolf
Enger Per Øyvind
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0607668103
Published
2006-10-31
Epub
2006-00-20
Pages
16466-71
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1618812
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0607668103 PMC Full Text View journal details
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