Angiogenesis-independent Tumor Growth Mediated by Stem-like Cancer Cells

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2006 Oct 24

PMID 17056721

Citations 101

Authors

Per O Sakariassen

Lars Prestegarden

Jian Wang

Kai-Ove Skaftnesmo

Rupavathana Mahesparan

Carla Molthoff

Peter Sminia

Eirik Sundlisaeter

Anjan Misra

Berit Bolge Tysnes

Martha Chekenya

Hans Peters

Gabriel Lende

Karl Henning Kalland

Anne M Oyan

Kjell Petersen

Inge Jonassen

Albert van der Kogel

Burt G Feuerstein

A Jorge A Terzis

Rolf Bjerkvig

Per Oyvind Enger

Affiliations

Soon will be listed here.

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.

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