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

Per Ø Sakariassen, Lars Prestegarden, Jian Wang, Kai-Ove Skaftnesmo, Rupavathana Mahesparan, Carla Molthoff, Peter Sminia, Eirik Sundlisaeter, Anjan Misra, Berit Bølge Tysnes, Martha Chekenya, Hans Peters, Gabriel Lende, Karl Henning Kalland, Anne M Øyan, Kjell Petersen, Inge Jonassen, Albert van der Kogel, Burt G Feuerstein, A Jorge A Terzis & 2 others Rolf Bjerkvig, Per Øyvind Enger

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)16466-71
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number44
DOIs
Publication statusPublished - 31 Oct 2006

Cite this

Sakariassen, P. Ø., Prestegarden, L., Wang, J., Skaftnesmo, K-O., Mahesparan, R., Molthoff, C., ... Enger, P. Ø. (2006). Angiogenesis-independent tumor growth mediated by stem-like cancer cells. Proceedings of the National Academy of Sciences of the United States of America, 103(44), 16466-71. https://doi.org/10.1073/pnas.0607668103
Sakariassen, Per Ø ; 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. / Angiogenesis-independent tumor growth mediated by stem-like cancer cells. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 44. pp. 16466-71.
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title = "Angiogenesis-independent tumor growth mediated by stem-like cancer cells",
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.",
keywords = "Animals, Biopsy, Chromosomes, Human/genetics, Disease Progression, Gene Expression Regulation, Humans, Immunohistochemistry, Neoplasm Invasiveness, Neoplasm Transplantation, Neoplasms/blood supply, Phenotype, Rats, Rats, Nude, Signal Transduction, Stem Cells, Survival Rate, Tumor Cells, Cultured",
author = "Sakariassen, {Per {\O}} and Lars Prestegarden and Jian Wang and Kai-Ove Skaftnesmo and Rupavathana Mahesparan and Carla Molthoff and Peter Sminia and Eirik Sundlisaeter and Anjan Misra and Tysnes, {Berit B{\o}lge} and Martha Chekenya and Hans Peters and Gabriel Lende and Kalland, {Karl Henning} and {\O}yan, {Anne M} and Kjell Petersen and Inge Jonassen and {van der Kogel}, Albert and Feuerstein, {Burt G} and Terzis, {A Jorge A} and Rolf Bjerkvig and Enger, {Per {\O}yvind}",
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Sakariassen, PØ, Prestegarden, L, Wang, J, Skaftnesmo, K-O, 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, AJA, Bjerkvig, R & Enger, PØ 2006, '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, pp. 16466-71. https://doi.org/10.1073/pnas.0607668103

Angiogenesis-independent tumor growth mediated by stem-like cancer cells. / Sakariassen, Per Ø; 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.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 44, 31.10.2006, p. 16466-71.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Angiogenesis-independent tumor growth mediated by stem-like cancer cells

AU - Sakariassen, Per Ø

AU - Prestegarden, Lars

AU - Wang, Jian

AU - Skaftnesmo, Kai-Ove

AU - Mahesparan, Rupavathana

AU - Molthoff, Carla

AU - Sminia, Peter

AU - Sundlisaeter, Eirik

AU - Misra, Anjan

AU - Tysnes, Berit Bølge

AU - Chekenya, Martha

AU - Peters, Hans

AU - Lende, Gabriel

AU - Kalland, Karl Henning

AU - Øyan, Anne M

AU - Petersen, Kjell

AU - Jonassen, Inge

AU - van der Kogel, Albert

AU - Feuerstein, Burt G

AU - Terzis, A Jorge A

AU - Bjerkvig, Rolf

AU - Enger, Per Øyvind

PY - 2006/10/31

Y1 - 2006/10/31

N2 - 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.

AB - 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.

KW - Animals

KW - Biopsy

KW - Chromosomes, Human/genetics

KW - Disease Progression

KW - Gene Expression Regulation

KW - Humans

KW - Immunohistochemistry

KW - Neoplasm Invasiveness

KW - Neoplasm Transplantation

KW - Neoplasms/blood supply

KW - Phenotype

KW - Rats

KW - Rats, Nude

KW - Signal Transduction

KW - Stem Cells

KW - Survival Rate

KW - Tumor Cells, Cultured

U2 - 10.1073/pnas.0607668103

DO - 10.1073/pnas.0607668103

M3 - Article

VL - 103

SP - 16466

EP - 16471

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 44

ER -