Netrin-1 Promotes Glioblastoma Cell Invasiveness and Angiogenesis by Multiple Pathways Including Activation of RhoA, Cathepsin B, and cAMP-response Element-binding Protein

Shimizu, Akio; Nakayama, Haruhiko; Wang, Priscilla; König, Courtney; Akino, Tomoshige; Sandlund, Johanna; Coma, Sílvia; Italiano, Joseph E.; Mammoto, Akiko; Bielenberg, Diane R.; Klagsbrun, Michael

doi:10.1074/jbc.m112.397398

Cited by 90 publications

(83 citation statements)

References 48 publications

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“…It has recently been suggested that NTN1 might function in a cell-autonomous manner to promote the movement/ detachment/release of progenitor cells from embryonic forebrain explants (Hakanen et al, 2011). Interestingly, a recent study pointed out a dual effect of NTN1 on glioblastoma progression by promoting both angiogenesis and invasiveness (Shimizu et al, 2012). A detachment effect of NTN1 could therefore contribute to enhancing progenitor cell emigration and recruitment at the lesion site.…”

Section: Discussionmentioning

confidence: 99%

Netrin 1 contributes to vascular remodeling in the subventricular zone and promotes progenitor emigration after demyelination

et al. 2013

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SUMMARYNeural stem cells are maintained in the adult brain, sustaining structural and functional plasticity and to some extent participating in brain repair. A thorough understanding of the mechanisms and factors involved in endogenous stem/progenitor cell mobilization is a major challenge in the promotion of spontaneous brain repair. The main neural stem cell niche in the adult brain is the subventricular zone (SVZ). Following demyelination insults, SVZ-derived progenitors act in concert with oligodendrocyte precursors to repopulate the lesion and replace lost oligodendrocytes. Here, we showed robust vascular reactivity within the SVZ after focal demyelination of the corpus callosum in adult mice, together with a remarkable physical association between these vessels and neural progenitors exiting from their niche. Endogenous progenitor cell recruitment towards the lesion was significantly reduced by inhibiting post-lesional angiogenesis in the SVZ using anti-VEGF blocking antibody injections, suggesting a facilitating role of blood vessels for progenitor cell migration towards the lesion. We identified netrin 1 (NTN1) as a key factor upregulated within the SVZ after demyelination and involved in local angiogenesis and progenitor cell migration. Blocking NTN1 expression using a neutralizing antibody inhibited both lesion-induced vascular reactivity and progenitor cell recruitment at the lesion site. We propose a model in which SVZ progenitors respond to a demyelination lesion by NTN1 secretion that both directly promotes cell emigration and contributes to local angiogenesis, which in turn indirectly facilitates progenitor cell emigration from the niche.

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Section: Discussionmentioning

confidence: 99%

Netrin 1 contributes to vascular remodeling in the subventricular zone and promotes progenitor emigration after demyelination

et al. 2013

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“…65,68 Whether these are also regulated by the netrin receptor DCC is unknown, but is possible given the strong association of netrin with metastatic cancers and invasive behavior in cell culture. [101][102][103][104] Importantly, after breaching basement membrane (a 2D flat, sheet-like surface), cancer cells often enter interstitial tissue, a largely acellular environment dominated by a less dense 3D network of fibrillar collagens. 105 This environment appears to trigger the formation of invadopodia-like structures that promote removal of interstitial matrix at points of cell restriction.…”

Section: Invadopodia Are Only One Component Of the Invasion Process Imentioning

confidence: 99%

Invadopodia and basement membrane invasion in vivo

Lohmer

Kelley

Hagedorn

et al. 2014

Cell Adhesion & Migration

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“…infiltration (Ohnishi et al, 1997;Ray et al, 2014;Reardon et al, 2008;Serres et al, 2014). In addition, increasing evidences suggest that neurovascular guidance cues, such as Eph/ephrin (Miao et al, 2015;Nakada et al, 2004;Wang et al, 2012), DCC/netrin (Jarjour et al, 2011;Shimizu et al, 2013;Ylivinkka et al, 2013), Robo/slit (Dallol et al, 2003;Mertsch et al, 2008;Yiin et al, 2009), Plexin/semaphorin (Bagci et al, 2009;Sabag et al, 2012;Zhou et al, 2012), are involved in glioma invasion. As an example, EphA2…”

Section: Accepted Manuscriptmentioning

confidence: 96%

A vascular perspective on neuronal migration

Segarra

Kirchmaier

Acker‐Palmer

2015

Mechanisms of Development

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During CNS development and adult neurogenesis, immature neurons travel from the germinal zones towards their final destination using cellular substrates for their migration. Classically, radial glia and neuronal axons have been shown to act as physical scaffolds to support neuroblast locomotion in processes known as gliophilic and neurophilic migration, respectively (Hatten, 1999; Marin and Rubenstein, 2003; Rakic, 2003). In adulthood, long distance neuronal migration occurs in a glial-independent manner since radial glia cells differentiate into astrocytes after birth. A series of studies highlight a novel mode of neuronal migration that uses blood vessels as scaffolds, the so-called vasophilic migration. This migration mode allows neuroblast navigation in physiological and also pathological conditions, such as neuronal precursor migration after ischemic stroke or cerebral invasion of glioma tumor cells. Here we review the current knowledge about how vessels pave the path for migrating neurons and how trophic factors derived by glio-vascular structures guide neuronal migration both during physiological as well as pathological processes.

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Netrin-1 Promotes Glioblastoma Cell Invasiveness and Angiogenesis by Multiple Pathways Including Activation of RhoA, Cathepsin B, and cAMP-response Element-binding Protein

Cited by 90 publications

References 48 publications

Netrin 1 contributes to vascular remodeling in the subventricular zone and promotes progenitor emigration after demyelination

Netrin 1 contributes to vascular remodeling in the subventricular zone and promotes progenitor emigration after demyelination

Invadopodia and basement membrane invasion in vivo

A vascular perspective on neuronal migration

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