The expanding role of neuropilin

Kofler, Natalie; Simons, Michael

doi:10.1097/moh.0000000000000233

Cited by 44 publications

(49 citation statements)

References 82 publications

(94 reference statements)

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“…Nrp1 as a TGFβ receptor signaling component has been reported previously in fibroblasts, endothelial cells and immune cells, and has been implicated as a driver of tumor progression [ 20 , 40 ]. Despite these findings, little is known about the mechanisms underlying Nrp1-mediated TGFβ signaling.…”

Section: Discussionmentioning

confidence: 99%

“…Nrp1 is a co-receptor for multiple secreted factors such as semaphorins [ 14 ], VEGF-A [ 15 ], HGF [ 16 ], Hedgehogs [ 17 ], EGF [ 18 ], and PDGFBB [ 19 ] and TGFβs [ 20 ]. Due to its numerous co-receptor roles, Nrp1 participates in pleiotropic functions in many organs in a cell type-selective manner to modulate proliferation, migration, and survival.…”

Section: Introductionmentioning

confidence: 99%

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Neuropilin-1 modulates TGFβ signaling to drive glioblastoma growth and recurrence after anti-angiogenic therapy

et al. 2017

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Glioblastoma (GBM) is a rapidly progressive brain cancer that exploits the neural microenvironment, and particularly blood vessels, for selective growth and survival. Anti-angiogenic agents such as the vascular endothelial growth factor-A (VEGF-A) blocking antibody bevacizumab yield short-term benefits to patients due to blood vessel regression and stabilization of vascular permeability. However, tumor recurrence is common, and this is associated with acquired resistance to bevacizumab. The mechanisms that drive acquired resistance and tumor recurrence in response to anti-angiogenic therapy remain largely unknown. Here, we report that Neuropilin-1 (Nrp1) regulates GBM growth and invasion by balancing tumor cell responses to VEGF-A and transforming growth factor βs (TGFβs). Nrp1 is expressed in GBM cells where it promotes TGFβ receptor internalization and signaling via Smad transcription factors. GBM that recur after bevacizumab treatment show down-regulation of Nrp1 expression, indicating that altering the balance between VEGF-A and TGFβ signaling is one mechanism that promotes resistance to anti-angiogenic agents. Collectively, these data reveal that Nrp1 plays a critical role in balancing responsiveness to VEGF-A versus TGFβ to regulate GBM growth, progression, and recurrence after anti-vascular therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Neuropilin-1 modulates TGFβ signaling to drive glioblastoma growth and recurrence after anti-angiogenic therapy

et al. 2017

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“…This suggests that PDGF-B secreted by endothelial cells binds to PDGFRβ of pericytes and vascular SMC, attracts them and induces their proliferation. Moreover, PDGF signaling in vascular SMC is regulated by neuropilin-1 and 2 [186] . It may be noted that the earliest stages of differentiation and migration of peri-endothelial progenitor cells to the angiogenic site require TGF-β-like factor synthesized by endothelial cells [33] .…”

Section: Mechanisms Of Plaque Neovascularizationmentioning

confidence: 99%

Angiogenesis in the atherosclerotic plaque

et al. 2017

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Atherosclerosis is a multifocal alteration of the vascular wall of medium and large arteries characterized by a local accumulation of cholesterol and non-resolving inflammation. Atherothrombotic complications are the leading cause of disability and mortality in western countries. Neovascularization in atherosclerotic lesions plays a major role in plaque growth and instability. The angiogenic process is mediated by classical angiogenic factors and by additional factors specific to atherosclerotic angiogenesis. In addition to its role in plaque progression, neovascularization may take part in plaque destabilization and thromboembolic events. Anti-angiogenic agents are effective to reduce atherosclerosis progression in various animal models. However, clinical trials with anti-angiogenic drugs, mainly anti-VEGF/VEGFR, used in anti-cancer therapy show cardiovascular adverse effects, and require additional investigations.

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“…The TGFβ superfamily member, Gdf10, was identified as a PA-enriched gene product. While glial-derived TGFβ signaling is important for angiogenesis and BBB formation during development [62], it remains uncertain if canonical TGFβ signaling in adult brain ECs is critical for BBB physiology. Gdf10 is also expressed by adult brain ECs and promotes astrocyte and neuronal survival as well as BBB repair following stroke [63].…”

Section: Discussionmentioning

confidence: 99%

Isolation and transcriptional characterization of mouse perivascular astrocytes

Yosef

McCarty

2020

PLoS ONE

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In the post-natal mammalian brain perivascular astrocytes (PAs) ensheath blood vessels to regulate their unique permeability properties known as the blood-brain barrier (BBB). Very little is known about PA-expressed genes and signaling pathways that mediate contact and communication with endothelial cells (ECs) to regulate BBB physiology. This is due, in part, to lack of suitable models to distinguish PAs from other astrocyte sub-populations in the brain. To decipher the unique biology of PAs, we used in vivo gene knock-in technology to fluorescently label these cells in the adult mouse brain followed by fractionation and quantitative single cell RNA sequencing. In addition, PAs and non-PAs were also distinguished with transgenic fluorescent reporters followed by gene expression comparisons using bulk RNA sequencing. These efforts have identified several genes and pathways in PAs with potential roles in contact and communication with brain ECs. These genes encode various extracellular matrix (ECM) proteins and adhesion receptors, secreted growth factors, and intracellular signaling enzymes. Collectively, our experimental data reveal a set of genes that are expressed in PAs with putative roles in BBB physiology.

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The expanding role of neuropilin

Cited by 44 publications

References 82 publications

Neuropilin-1 modulates TGFβ signaling to drive glioblastoma growth and recurrence after anti-angiogenic therapy

Neuropilin-1 modulates TGFβ signaling to drive glioblastoma growth and recurrence after anti-angiogenic therapy

Angiogenesis in the atherosclerotic plaque

Isolation and transcriptional characterization of mouse perivascular astrocytes

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