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.
authors.affiliation: NorLux NeuroOncology, Department of Biomedicine, University of Bergen, N-5020 Bergen, Norway.
authors.forename: Per Ø
authors.initials: PØ
authors.lastname: Sakariassen
authors.forename: Lars
authors.initials: L
authors.lastname: Prestegarden
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Kai-Ove
authors.initials: KO
authors.lastname: Skaftnesmo
authors.forename: Rupavathana
authors.initials: R
authors.lastname: Mahesparan
authors.forename: Carla
authors.initials: C
authors.lastname: Molthoff
authors.forename: Peter
authors.initials: P
authors.lastname: Sminia
authors.forename: Eirik
authors.initials: E
authors.lastname: Sundlisaeter
authors.forename: Anjan
authors.initials: A
authors.lastname: Misra
authors.forename: Berit Bølge
authors.initials: BB
authors.lastname: Tysnes
authors.forename: Martha
authors.initials: M
authors.lastname: Chekenya
authors.forename: Hans
authors.initials: H
authors.lastname: Peters
authors.forename: Gabriel
authors.initials: G
authors.lastname: Lende
authors.forename: Karl Henning
authors.initials: KH
authors.lastname: Kalland
authors.forename: Anne M
authors.initials: AM
authors.lastname: Øyan
authors.forename: Kjell
authors.initials: K
authors.lastname: Petersen
authors.forename: Inge
authors.initials: I
authors.lastname: Jonassen
authors.forename: Albert
authors.initials: A
authors.lastname: van der Kogel
authors.forename: Burt G
authors.initials: BG
authors.lastname: Feuerstein
authors.forename: A Jorge A
authors.initials: AJ
authors.lastname: Terzis
authors.forename: Rolf
authors.initials: R
authors.lastname: Bjerkvig
authors.forename: Per Øyvind
authors.initials: PØ
authors.lastname: Enger
mesh_terms: D000818:Animals; D001706:Biopsy; D002877:Chromosomes, Human / Q000235:genetics; D018450:Disease Progression; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology*; D010641:Phenotype; D051381:Rats; D011923:Rats, Nude; D015398:Signal Transduction; D013234:Stem Cells; D015996:Survival Rate; D014407:Tumor Cells, Cultured