The neuropilins and their role in tumorigenesis and tumor progression

Guttmann‐Raviv, Noga; Kessler, Ofra; Shraga-Heled, Niva; Lange, Tali; Herzog, Yael; Neufeld, Gera

doi:10.1016/j.canlet.2004.12.047

Cited by 134 publications

(97 citation statements)

References 81 publications

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“…[20][21][22][23] NRPs are also highly expressed in diverse tumor cell lines and human neoplasms and have been implicated in tumor growth and vascularization. [2][3][4]24,25 More recently, it has been reported that NRP1 might have a role as a novel mediator of the primary immune response, as well as in tissue regeneration and repair. 26 Together these findings suggest that NRPs are multifunctional co-receptors essential for neuronal and cardiovascular development, but potentially have additional functions in diverse physiological and disease-related settings.…”

Section: Discussionmentioning

confidence: 99%

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Neuropilin-1 and neuropilin-2 are differentially expressed in human proteinuric nephropathies and cytokine-stimulated proximal tubular cells

Schramek

Sarközi

Lauterberg

et al. 2009

Laboratory Investigation

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Neuropilin-1 (NRP1) and neuropilin-2 (NRP2) are transmembrane glycoproteins with large extracellular domains that interact with class 3 semaphorins, vascular endothelial growth factor (VEGF) family members, and ligands, such as hepatocyte growth factor, platelet-derived growth factor BB, transforming growth factor-b1 (TGF-b1), and fibroblast growth factor2 (FGF2). Neuropilins (NRPs) have been implicated in tumor growth and vascularization, as novel mediators of the primary immune response and in regeneration and repair; however, their role in renal pathophysiology is largely unknown. Here, we report upregulation of tubular and interstitial NRP2 protein expression in patients with focal segmental glomerulosclerosis (FSGS). In an additional cohort of patients with minimal change disease (MCD), membranous nephropathy (MN), and FSGS, elevated NRP2 mRNA expression in kidney biopsies inversely correlated with estimated glomerular filtration rate (eGFR) at the time of biopsy. Furthermore, upregulation of NRP2 mRNA correlated with post-bioptic decline of kidney function. Expression of NRP1 and NRP2 in human proximal tubular cells (PTCs) was differentially affected after stimulation with TGF-b1, interleukin-1b (IL-1b), and oncostatin M (OSM). Although the pro-fibrotic mediators, TGF-b1 and IL-1b, induced upregulation of NRP2 expression but downregulation of NRP1 expression, OSM stimulated the expression of both NRP1 and NRP2. Basal and OSM-induced NRP1 mRNA expression, as well as TGF-b1-induced NRP2 mRNA and protein expression were partially mediated by MEK1/2-ERK1/2 signaling. This is the first report suggesting a differential role of NRP1 and NRP2 in renal fibrogenesis, and TGF-b1, IL-1b, and OSM represent the first ligands known to stimulate NRP2 expression in mammalian cells.

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Section: Discussionmentioning

confidence: 99%

“…[8][9][10] The cells (passages [20][21][22][23][24][25][26][27][28][29][30] were grown at 371C in a humidified 5% CO 2 atmosphere, and split at a 1:10 ratio, once a week. After growth to a subconfluent state, cells were washed once, made quiescent by incubation in serum-and supplementfree medium for 48 h, and then used for experiments.…”

Section: Cell Culturementioning

confidence: 99%

Neuropilin-1 and neuropilin-2 are differentially expressed in human proteinuric nephropathies and cytokine-stimulated proximal tubular cells

Schramek

Sarközi

Lauterberg

et al. 2009

Laboratory Investigation

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“…Neuropilin receptors are thought to modulate VEGF signaling through VEGFR-1 and VEGFR-2. 33 In 1 series, 80% of osteosarcoma samples expressed neuropilin-2 mRNA. Patients with neuropilin-2 tumor expression had decreased overall survival compared with patients without neuropilin-2 tumor expression.…”

Section: Skeletal Sarcomasmentioning

confidence: 99%

“…32 Unlike VEGFR-1 and VEGFR-2, which can bind any of the VEGF isoforms, the neuropilin family of receptors demonstrate VEGF isoform-specific binding. 33 Neuropilin-2 binds VEGF145 and VEGF165, but not VEGF121. Neuropilin receptors are thought to modulate VEGF signaling through VEGFR-1 and VEGFR-2.…”

Section: Skeletal Sarcomasmentioning

confidence: 99%

Markers of angiogenesis and clinical features in patients with sarcoma

DuBois

Demetri

2007

Cancer

128

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Objective: Patient outcome after traumatic brain injury (TBI) is highly variable. The underlying pathophysiology of this is poorly understood, but inflammation is potentially an important factor. Microglia orchestrate many aspects of this response. Their activation can be studied in vivo using the positron emission tomography (PET) ligand [11C](R)PK11195 (PK). In this study, we investigate whether an inflammatory response to TBI persists, and whether this response relates to structural brain abnormalities and cognitive function. Methods: Ten patients, studied at least 11 months after moderate to severe TBI, underwent PK PET and structural magnetic resonance imaging (including diffusion tensor imaging). PK binding potentials were calculated in and around the site of focal brain damage, and in selected distant and subcortical brain regions. Standardized neuropsychological tests were administered. Results: PK binding was significantly raised in the thalami, putamen, occipital cortices, and posterior limb of the internal capsules after TBI. There was no increase in PK binding at the original site of focal brain injury. High PK binding in the thalamus was associated with more severe cognitive impairment, although binding was not correlated with either the time since the injury or the extent of structural brain damage. Interpretation: We demonstrate that increased microglial activation can be present up to 17 years after TBI. This suggests that TBI triggers a chronic inflammatory response particularly in subcortical regions. This highlights the importance of considering the response to TBI as evolving over time and suggests interventions may be beneficial for longer intervals after trauma than previously assumed. ANN NEUROL 2011;

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“…74 Clinical studies suggest that NP-1 plays a role in tumor growth and disease progression due to mediating VEGF signals. 75,76 Recent studies have shown that semaphorins are secreted from tumor cells as well as macrophages and fibroblasts in the tumor microenvironment, thereby influencing cancers and their microenvironments. For instance, Sema3A is secreted from tumors or ECs and suppresses the adhesion and migration of tumor cells and ECs by modulating integrin activities.…”

Section: Sema7a: a Semaphorin Involved In Inflammatory Responses Via mentioning

confidence: 99%

Regulation of immune cell responses by semaphorins and their receptors

2010

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Semaphorins were originally identified as axon guidance factors involved in the development of the neuronal system. However, accumulating evidence indicates that several members of semaphorins, so-called 'immune semaphorins', are crucially involved in various phases of immune responses. These semaphorins regulate both immune cell interactions and immune cell trafficking during physiological and pathological immune responses. Here, we review the following two functional aspects of semaphorins and their receptors in immune responses: their functions in cell-cell interactions and their involvement in immune cell trafficking.

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The neuropilins and their role in tumorigenesis and tumor progression

Cited by 134 publications

References 81 publications

Neuropilin-1 and neuropilin-2 are differentially expressed in human proteinuric nephropathies and cytokine-stimulated proximal tubular cells

Neuropilin-1 and neuropilin-2 are differentially expressed in human proteinuric nephropathies and cytokine-stimulated proximal tubular cells

Markers of angiogenesis and clinical features in patients with sarcoma

Regulation of immune cell responses by semaphorins and their receptors

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