Angiogenesis in brain tumours

Jain, Rakesh K.; Tomaso, Emmanuelle di; Duda, Dan G.; Loeffler, Jay S.; Sorensen, A. Gregory; Batchelor, Tracy T.

doi:10.1038/nrn2175

Cited by 1,225 publications

(1,136 citation statements)

References 135 publications

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“…To the best of our knowledge, this is the first study to characterize the vascular phenotype of a mouse brain tumor model with mMRI. We showed that (Jain et al, 2007;Vajkoczy and Menger, 2000). Our results also show characteristic differences between the vasculatures of D12 and D17 tumors.…”

Section: Discussionsupporting

confidence: 73%

“…Knowledge of the three-dimensional (3D) architecture of blood vessels is crucial for several reasons: (1) Various neuropathologies ranging from Alzheimer's disease to brain tumors involve anomalous blood vessels (Iadecola, 2004;Jain et al, 2007). (2) The physiologic basis of image contrast in functional magnetic resonance imaging critically depends on the underlying microvasculature (Moonen et al, 1990;Pathak et al, 2003Pathak et al, , 2008c.…”

Section: Introductionmentioning

confidence: 99%

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Vascular phenotyping of brain tumors using magnetic resonance microscopy (μMRI)

Kim

Zhang

Hong

et al. 2011

J Cereb Blood Flow Metab

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Abnormal vascular phenotypes have been implicated in neuropathologies ranging from Alzheimer's disease to brain tumors. The development of transgenic mouse models of such diseases has created a crucial need for characterizing the murine neurovasculature. Although histologic techniques are excellent for imaging the microvasculature at submicron resolutions, they offer only limited coverage. It is also challenging to reconstruct the three-dimensional (3D) vasculature and other structures, such as white matter tracts, after tissue sectioning. Here, we describe a novel method for 3D whole-brain mapping of the murine vasculature using magnetic resonance microscopy (lMRI), and its application to a preclinical brain tumor model. The 3D vascular architecture was characterized by six morphologic parameters: vessel length, vessel radius, microvessel density, length per unit volume, fractional blood volume, and tortuosity. Region-of-interest analysis showed significant differences in the vascular phenotype between the tumor and the contralateral brain, as well as between postinoculation day 12 and day 17 tumors. These results unequivocally show the feasibility of using lMRI to characterize the vascular phenotype of brain tumors. Finally, we show that combining these vascular data with coregistered images acquired with diffusion-weighted MRI provides a new tool for investigating the relationship between angiogenesis and concomitant changes in the brain tumor microenvironment.

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Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Vascular phenotyping of brain tumors using magnetic resonance microscopy (μMRI)

Kim

Zhang

Hong

et al. 2011

J Cereb Blood Flow Metab

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“…Vasculogenesis was traditionally considered an embryonic process but has since been identified to occur in several tumor types (Lyden et al, 2001) including brain tumors (SantarelLi et al, 2006;Zhang et al, 2009). Vasculogenesis involves the de novo formation of blood vessels that utilize bone marrow-derived endothelial progenitor cells (Jain et al, 2007). Angiogenesis is the production of new blood vessels by endothelial cells from pre-existing vessels and is considered to be the primary mode of vessel formation in gliomas (Tate and Aghi, 2009).…”

Section: Brain Tumor Stem-like Cellsmentioning

confidence: 99%

The brain tumor microenvironment

Charles

Holland

Gilbertson

et al. 2011

Glia

687

327

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High-grade brain tumors are heterogeneous with respect to the composition of bona fide tumor cells and with respect to a range of intermingling parenchymal cells. Glioblastomas harbor multiple cell types, some with increased tumorigenicity and stem cell-like capacity. The stem-like cells may be the cells of origin for tumor relapse. However, the tumor-associated parenchymal cells such as vascular cells, microglia, peripheral immune cells, and neural precursor cells also play a vital role in controlling the course of pathology. In this review, we describe the multiple interactions of bulk glioma cells and glioma stem cells with parenchymal cell populations and highlight the pathological impact as well as signaling pathways known for these types of cell-cell communication. The tumor-vasculature not only nourishes glioblastomas, but also provides a specialized niche for these stem-like cells. In addition, microglial cells, which can contribute up to 30% of a brain tumor mass, play a role in glioblastoma cell invasion. Moreover, non-neoplastic astrocytes can be converted into a reactive phenotype by the glioma microenvironment and can then secrete a number of factors which influences tumor biology. The young brain may have the capacity to inhibit gliomagenesis by the endogenous neural precursor cells, which secrete tumor suppressive factors. The factors, pathways, and interactions described in this review provide a new prospective on the cell biology of primary brain tumors, which may ultimately generate new treatment modalities. However, our picture of the multiple interactions between parenchymal and tumor cells is still incomplete. V

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“…GSC maintenance and fate rely upon external regulatory interactions with the brain microenvironment, of which vascular niche is thought to play a critical role [13]. Indeed, both the proximity to capillaries and pro-angiogenic activity of GSCs suggest the existence of crucial communication pathways between these cells and the endothelium [14,15]. …”

Section: Introductionmentioning

confidence: 99%

Molecular subtypes and differentiation programmes of glioma stem cells as determinants of extracellular vesicle profiles and endothelial cell‐stimulating activities

Spinelli

Montermini

Meehan

et al. 2018

J of Extracellular Vesicle

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We have previously uncovered the impact of oncogenic and differentiation processes on extracellular vesicles (EVs) in cancer. This is of interested in the context of glioma stem cells (GSC) that are responsible for recurrent nature of glioblastoma multiforme (GBM), while retaining the potential to undergo differentiation and self renewal. GSCs reside in vascular niches where they interact with endothelial cells through a number of mediators including bioactive cargo of EVs. GSCs can be classified as proneural (PN) or mesenchymal (MES) subtypes on the basis of their gene expression profiles and distinct biological characteristics. In the present study we investigated how GSC diversity and differentiation programmes influence their EV-mediated communication potentials. Indeed, molecular subtypes of GBMs and GSCs differ with respect to their expression of EV-related genes (vesiculome) and GSCs with PN or MES phenotypes produce EVs with markedly different characteristics, marker profiles, proteomes and endothelial stimulating activities. For example, while EVs of PN GSC are largely devoid of exosomal markers their counterparts from MES GSCs express ample CD9, CD63 and CD81 tetraspanins. In both GSC subtypes serum-induced differentiation results in profound, but distinct changes of cellular phenotypes including the enhanced EV production, reconfiguration of their proteomes and the related functional pathways. Notably, the EV uptake was a function of both subtype and differentiation state of donor cells. Thus, while, EVs produced by differentiated MES GSCs were internalized less efficiently than those from undifferentiated cells they exhibited an increased stimulatory potential for human brain endothelial cells. Such stimulating activity was also observed for EVs derived from differentiated PN GSCs, despite their even weaker uptake by endothelial cells. These findings suggest that the role of EVs as biological mediators and biomarkers in GBM may depend on the molecular subtype and functional state of donor cancer cells, including cancer stem cells.Abbreviations: CryoTEM: cryo-transmission electron microscopy; DIFF: differentiated GSCs; EGF: epidermal growth factor; DUC: differential ultracentrifugation; EV: extracellular vesicle; FGF: fibroblast growth factor; GBM: glioblastoma multiforme; GFAP: glial fibrillary acidic protein; GO: gene ontology; GSC: glioma stem cells; HBEC-5i: human brain endothelial cells; MES: mesenchymal cells; MTS - [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt; PMT1: proneural-to-mesenchyman transition cell line 1; PN: proneural cells; TEM: transmission electron microscopy; WB: western blotting

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Angiogenesis in brain tumours

Cited by 1,225 publications

References 135 publications

Vascular phenotyping of brain tumors using magnetic resonance microscopy (μMRI)

Vascular phenotyping of brain tumors using magnetic resonance microscopy (μMRI)

The brain tumor microenvironment

Molecular subtypes and differentiation programmes of glioma stem cells as determinants of extracellular vesicle profiles and endothelial cell‐stimulating activities

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