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https://www.readbyqxmd.com/read/29898965/b7-h4-modulates-regulatory-cd4-t-cell-induction-and-function-via-ligation-of-a-semaphorin-3a-plexin-a4-neuropilin-1-complex
#1
Joseph R Podojil, Ming-Yi Chiang, Igal Ifergan, Ronald Copeland, Linda N Liu, Sebastien Maloveste, Solomon Langermann, David Liebenson, Roumen Balabanov, Hongbo Chi, Lieping Chen, Dario A A Vignali, Stephen D Miller
The potent immune regulatory function of an agonistic B7-H4-Ig fusion protein (B7-H4Ig) has been demonstrated in multiple experimental autoimmune models; however, the identity of a functional B7-H4 receptor remained unknown. The biological activity of B7-H4 is associated with decreased inflammatory CD4+ T cell responses as supported by a correlation between B7-H4-expressing tumor-associated macrophages and Foxp3+ T cells within the tumor microenvironment. Recent data indicate that members of the semaphorin (Sema)/plexin/neuropilin (Nrp) family of proteins both positively and negatively modulate immune cell function...
June 13, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29885416/nanodisk-based-glioma-targeted-drug-delivery-enabled-by-a-stable-glycopeptide
#2
Huan Wang, Xiaoyi Wang, Cao Xie, Mingfei Zhang, Huitong Ruan, Songli Wang, Kuan Jiang, Fei Wang, Changyou Zhan, Weiyue Lu, Hao Wang
Heptapeptide ATWLPPR (A7R) binds specifically to vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1) overexpressed in glioma cells, exhibiting high potential to achieve glioma targeted drug delivery. However, in vivo application of A7R peptide remains challenging due to the poor proteolytic stability and inaccessibility of A7R to the brain. To tackle these problems, we identified a glycosylated A7R derivative to enhance in vivo stability and brain transport efficacy. Our results showed that glycosylation of peptide could efficiently improve stability in serum, traverse the blood-brain barrier (BBB) and be uptaken by glioma cells...
June 6, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29880492/vegf-vascular-endothelial-growth-factor-induces-nrp1-neuropilin-1-cleavage-via-adams-a-disintegrin-and-metalloproteinase-9-and-10-to-generate-novel-carboxy-terminal-nrp1-fragments-that-regulate-angiogenic-signaling
#3
Vedanta Mehta, Laura Fields, Ian M Evans, Maiko Yamaji, Caroline Pellet-Many, Timothy Jones, Marwa Mahmoud, Ian Zachary
OBJECTIVE: NRP1(neuropilin-1) acts as a coreceptor for VEGF (vascular endothelial growth factor) with an essential role in angiogenesis. Recent findings suggest that posttranslational proteolytic cleavage of VEGF receptors may be an important mechanism for regulating angiogenesis, but the role of NRP1 proteolysis and the NRP1 species generated by cleavage in endothelial cells is not known. To characterize NRP1 proteolytic cleavage in endothelial cells, determine the mechanism, and investigate the role of NRP1 cleavage in regulation of endothelial cell function...
June 7, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29873058/immunohistochemical-study-on-neuropilin-1-nrp1-immunoexpression-in-oral-squamous-cell-carcinoma
#4
Olga Stasikowska-Kanicka, Małgorzata Wągrowska-Danilewicz, Marian Danilewicz
INTRODUCTION: Neuropilins (NRPs) are multifunctional glycoproteins that play an important role in angiogenesis and cancer progression. The aim of the study was to examine the immunoexpression of neuropilin 1 (NRP1), the number of NRP1+ infiltrating cells and CD163+ macrophages, and density of microvessels (MVD) in oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: . The study was performed on 45 OSCC patients with metastases (OSCCM+), 51 patients without metastases (OSCCM-) and 17 control cases...
June 6, 2018: Folia Histochemica et Cytobiologica
https://www.readbyqxmd.com/read/29872627/enhanced-glioma-targeting-and-stability-of-l-gicp-peptide-coupled-with-stabilized-peptide-d-a7r
#5
Mingfei Zhang, Weiyue Lu
Malignant glioma is usually accompanied by vigorous angiogenesis to provide essential nutrients. An effective glioma targeting moiety should include excellent tumor-cell homing ability as well as good neovasculature-targeting efficiency, and should be highly resistant to enzyme degradation in the bloodstream. The phage display-selected heptapeptide, the glioma-initiating cell peptide (GICP), was previously reported as a ligand for the VAV3 protein (a Rho-GTPase guanine nucleotide exchange factor), which is mainly expressed on glioma cells; the stabilized heptapeptide D A7R has been shown to be the ligand of both vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1), and has demonstrated good neovasculature-targeting ability...
January 2018: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/29858743/roles-of-prostaglandins-in-tumor-associated-lymphangiogenesis-with-special-reference-to-breast-cancer
#6
Peeyush K Lala, Pinki Nandi, Mousumi Majumder
Lymphangiogenesis (formation of new lymphatic vessels), unlike angiogenesis, has been a lesser-focused field in cancer biology, because of earlier controversy regarding whether lymphatic metastasis occurs via pre-existing or newly formed lymphatics. Recent evidence reveals that peri-tumoral or intra-tumoral lymphangiogenesis is a precursor for lymphatic metastasis in most carcinomas and melanomas. Two major lymphangiogenic factors, vascular endothelial growth factor (VEGF)-C and VEGF-D, are produced by cancer cells or immune cells such as macrophages in the tumor-stroma to promote sprouting of lymphatics from lymphatic endothelial cells (LEC) or LEC precursors (LECP) by binding to their primary (high affinity) receptor VEGF-R3 or secondary receptors VEGF-R2, neuropilin (NRP)2 and α9/β1 integrin...
June 1, 2018: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/29849784/lymphatics-associated-genes-are-downregulated-at-transcription-level-in-non-small-cell-lung-cancer
#7
Oksana Kowalczuk, Jerzy Laudanski, Wojciech Laudanski, Wieslawa Ewa Niklinska, Miroslaw Kozlowski, Jacek Niklinski
The present study aimed to verify a possibility of ongoing lymphangiogenesis in non-small cell lung cancer (NSCLC) via examination of mRNA levels of a number of lymphangiogenesis-associated genes in tumors. It was hypothesized that transcriptional activation of these genes would occur in tumors that stimulate new lymphatic vessel formation. The study was performed on 140 pairs of fresh-frozen surgical specimens of cancer and unaffected lung tissues derived from NSCLC stage I-IIIA patients. mRNA levels were evaluated with the reverse transcription-quantitative polymerase chain reaction method and expressed as fold change differences between the tumor and normal tissues...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29849491/semaphorin-3a-inhibits-inflammation-in-chondrocytes-under-excessive-mechanical-stress
#8
Chikako Sumi, Naoto Hirose, Makoto Yanoshita, Mami Takano, Sayuri Nishiyama, Yuki Okamoto, Yuki Asakawa, Kotaro Tanimoto
Background: Excessive mechanical stress causes inflammation and destruction of cartilage and is considered one of the cause of osteoarthritis (OA). Expression of semaphorin 3A (Sema3A), which is an axon guidance molecule, has been confirmed in chondrocytes. However, there are few reports about Sema3A in chondrocytes, and the effects of Sema3A on inflammation in the cartilage are poorly understood. The aim of this study was to examine the role of Sema3A in inflammation caused by high magnitude cyclic tensile strain (CTS)...
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29794061/a-rationally-designed-nrp1-independent-superagonist-sema3a-mutant-is-an-effective-anticancer-agent
#9
Noemi Gioelli, Federica Maione, Chiara Camillo, Michela Ghitti, Donatella Valdembri, Noemi Morello, Marie Darche, Lorena Zentilin, Gabriella Cagnoni, Yaqi Qiu, Mauro Giacca, Maurizio Giustetto, Michel Paques, Ilaria Cascone, Giovanna Musco, Luca Tamagnone, Enrico Giraudo, Guido Serini
Vascular normalizing strategies, aimed at ameliorating blood vessel perfusion and lessening tissue hypoxia, are treatments that may improve the outcome of cancer patients. Secreted class 3 semaphorins (SEMA3), which are thought to directly bind neuropilin (NRP) co-receptors that, in turn, associate with and elicit plexin (PLXN) receptor signaling, are effective normalizing agents of the cancer vasculature. Yet, SEMA3A was also reported to trigger adverse side effects via NRP1. We rationally designed and generated a safe, parenterally deliverable, and NRP1-independent SEMA3A point mutant isoform that, unlike its wild-type counterpart, binds PLXNA4 with nanomolar affinity and has much greater biochemical and biological activities in cultured endothelial cells...
May 23, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29794036/deep-phenotyping-in-zebrafish-reveals-genetic-and-diet-induced-adiposity-changes-that-may-inform-disease-risk
#10
James E N Minchin, Catherine M Scahill, Nicole Staudt, Elisabeth M Busch-Nentwich, John F Rawls
The regional distribution of adipose tissues is implicated in a wide range of diseases. For example, proportional increases in visceral adipose tissue increase the risk for insulin resistance, diabetes and cardiovascular disease. Zebrafish offer a tractable model system by which to obtain unbiased and quantitative phenotypic information on regional adiposity, and deep phenotyping can explore complex disease-related adiposity traits. To facilitate deep phenotyping of zebrafish adiposity traits, we used pairwise correlations between 67 adiposity traits to generate stage-specific adiposity profiles that describe changing adiposity patterns and relationships during growth...
May 23, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29790686/the-expression-of-selected-molecular-markers-of-immune-tolerance-in-psoriatic-patients
#11
Joanna Bartosińska, Joanna Purkot, Małgorzata Kowal, Anna Michalak-Stoma, Dorota Krasowska, Grażyna Chodorowska, Krzysztof Giannopoulos
BACKGROUND: Psoriasis is a chronic autoinflammatory disease whose underlying molecular mechanisms remain unclear. The disease is mediated by the cells and molecules of both the innate and adaptive immune systems. Some T cell surface molecules, including neuropilin-1 (NRP1), programmed death 1 (PD-1) and the human leukocyte antigen G (HLA-G), are known to play a role in the maintenance of immune tolerance. OBJECTIVES: The aim of this study was to investigate HLA-G, NRP1 and programmed cell death gene (PDCD1) mRNA expression in psoriatic patients...
April 24, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29779877/developmental-upregulation-of-ephrin-b1-silences-sema3c-neuropilin-1-signaling-during-post-crossing-navigation-of-corpus-callosum-axons
#12
Erik Mire, Mélanie Hocine, Elsa Bazellières, Thomas Jungas, Alice Davy, Sophie Chauvet, Fanny Mann
The corpus callosum is the largest commissure in the brain, whose main function is to ensure communication between homotopic regions of the cerebral cortex. During fetal development, corpus callosum axons (CCAs) grow toward and across the brain midline and then away on the contralateral hemisphere to their targets. A particular feature of this circuit, which raises a key developmental question, is that the outgoing trajectory of post-crossing CCAs is mirror-symmetric with the incoming trajectory of pre-crossing axons...
May 10, 2018: Current Biology: CB
https://www.readbyqxmd.com/read/29777301/role-of-the-nrp-1-mediated-vegfr2-independent-pathway-on-radiation-sensitivity-of-non-small-cell-lung-cancer-cells
#13
Chenxi Hu, Panrong Zhu, Youyou Xia, Kaiyuan Hui, Mei Wang, Xiaodong Jiang
PURPOSE: To determine if inhibiting neuropilin-1 (NRP-1) affects the radiosensitivity of NSCLC cells through a vascular endothelial growth factor receptor 2 (VEGFR2)-independent pathway, and to assess the underlying mechanisms. METHODS: The expression of VEGFR2, NRP-1, related signaling molecules, abelson murine leukemia viral oncogene homolog 1 (ABL-1), and RAD51 were determined by RT-PCR and Western blotting, respectively. Radiosensitivity was assessed using the colony-forming assay, and the cell apoptosis were analyzed by flow cytometry...
May 17, 2018: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29774910/design-of-rgd-atwlppr-peptide-conjugates-for-the-dual-targeting-of-%C3%AE-v-%C3%AE-3-integrin-and-neuropilin-1
#14
Fabien Thoreau, Laetitia Vanwonterghem, Maxime Henry, Jean-Luc Coll, Didier Boturyn
Targeting the tumour microenvironment is a promising strategy to detect and/or treat cancer. The design of selective compounds that co-target several receptors frequently overexpressed in solid tumours may allow a reliable and selective detection of tumours. Here we report the modular synthesis of compounds encompassing ligands of αVβ3 integrin and neuropilin-1 that are overexpressed in the tumour microenvironment. These compounds were then evaluated through cellular experiments and imaging of tumours in mice...
May 18, 2018: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/29773756/mir126-5p-down-regulation-facilitates-axon-degeneration-and-nmj-disruption-via-a-non-cell-autonomous-mechanism-in-als
#15
Roy Maimon, Ariel Ionescu, Avichai Bonnie, Sahar Sweetat, Shane Wald-Altman, Shani Inbar, Tal Gradus, Davide Trotti, Miguel Weil, Oded Behar, Eran Perlson
Axon degeneration and disruption of neuromuscular junctions (NMJs) are key events in Amyotrophic Lateral Sclerosis (ALS) pathology. Although the disease's etiology is not fully understood, it is thought to involve a non-cell-autonomous mechanism and alterations in RNA metabolism. Here, we identified reduced levels of miR-126-5p in pre-symptomatic ALS male mice models, and an increase in its targets: axon destabilizing type-3 Semaphorins and their co-receptor Neuropilins. Utilizing compartmentalized in vitro co-cultures, we demonstrated that myocytes expressing diverse ALS-causing mutations promote axon degeneration and NMJ dysfunction, which were inhibited by applying Neuropilin1 (NRP1) blocking antibody...
May 17, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29755126/nrp-1-interacts-with-gipc1-and-%C3%AE-6-%C3%AE-4-integrins-to-increase-yap1-%C3%A2-np63%C3%AE-dependent-epidermal-cancer-stem-cell-survival
#16
Daniel Grun, Gautam Adhikary, Richard L Eckert
We have identified an epidermal cancer stem (ECS) cell population that drives formation of rapidly growing and highly invasive and vascularized tumors. VEGF-A and neuropilin-1 (NRP-1) are highly expressed in ECS cell tumors and VEGF-A/NRP-1 interaction is required for ECS cell survival and tumor vascularization. We now identify a novel signaling cascade that is triggered by VEGF-A/NRP-1. We show that NRP-1 forms a complex with GIPC1 and α6/β4-integrin to activate FAK/Src signaling, which leads to stabilization of a YAP1/∆Np63α to enhance ECS cell survival, invasion, and angiogenesis...
May 14, 2018: Oncogene
https://www.readbyqxmd.com/read/29750423/nrp1-knockdown-promotes-the-migration-and-invasion-of-human-neuroblastoma-derived-sk%C3%A2-n%C3%A2-as-cells-via-the-activation-of-%C3%AE-1-integrin-expression
#17
Yoshiaki Ishizuka, Tsugumichi Koshinaga, Takayuki Hirano, Eri Nagasaki-Maeoka, Yosuke Watanabe, Reina Hoshi, Shinsuke Yoshizawa, Kiminobu Sugito, Hiroyuki Kawashima, Shota Uekusa, Noboru Fukuda, Masayoshi Soma, Kyoko Fujiwara
Neuropilin 1 (NRP1) is a transmembrane glycoprotein, which regulates many aspects of cellular function by functioning as co-receptor of various ligands. Recent studies have suggested that NRP1 promotes tumorigenesis, not only by activating the growth of tumor vessels, but also by activating the growth or migration of tumor cells themselves. The present study was performed to elucidate the roles of NRP1 in the development and/or progression of neuroblastoma (NB). In contrast to previous observations in various types of cancer, the analysis of public datasets indicated that lower levels of NRP1 expression were significantly associated with a shorter survival period of patients with NB...
May 7, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29734808/enhanced-glioblastoma-targeting-ability-of-carfilzomib-enabled-by-d-a7r-modified-lipid-nanodisk
#18
Mingfei Zhang, Linwei Lu, Man Ying, Huitong Ruan, Xiaoyi Wang, Huan Wang, Zhilan Chai, Songli Wang, Changyou Zhan, Jun Pan, Weiyue Lu
The robust proliferation of tumors relies on rich neovasculature for nutrients supply. Therefore, a basic strategy of tumor targeting therapy should include not only killing regular cancer cells but also blocking tumor neovasculature. D-peptide DA7R, which was previously reported to specifically bind vascular endothelial growth factor receptor 2 (VEGFR2) and neuropilin-1 (NRP-1), could achieve the goal of multi-targets recognition. Accordingly, the main purposes of this work were to establish a carfilzomib loaded lipid nanodisk modified with multifunctional peptide DA7R (DA7R-ND/CFZ) and to evaluate its anti-glioblastoma efficacy in vitro and in vivo...
May 7, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29730556/new-peptide-my1340-revert-the-inhibition-effect-of-vegf-on-dendritic-cells-differentiation-and-maturation-via-blocking-vegf-nrp-1-axis-and-inhibit-tumor-growth-in-vivo
#19
Zheng Mo, Fei Yu, Su Han, Songhua Yang, Liangliang Wu, Peng Li, Shunchang Jiao
The development and clinical application of immunostimulatory therapy provides us a new and exciting strategy in cancer treatment of which the agents act on crucial receptors. Given the fact that Neuropilin-1(NRP-1) is essential for vascular endothelial growth factor (VEGF) to inhibit LPS-dependent maturation of dendritic cells (DCs), it may present a potentially meaningful target in cancer immunotherapy. To explore this hypothesis, we synthesized a novel polypeptide called MY1340 consist of 32 amino acids with the aim of targeting VEGF-NRP-1 axis...
May 3, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29728574/pathological-conversion-of-regulatory-t-cells-is-associated-with-loss-of-allotolerance
#20
Jing Hua, Takenori Inomata, Yihe Chen, William Foulsham, William Stevenson, Tina Shiang, Jeffrey A Bluestone, Reza Dana
CD4+ CD25+ Foxp3+ Regulatory T cells (Tregs) play a critical role in immune tolerance. The plasticity and functional adaptability of Tregs in an inflammatory microenvironment has been demonstrated in autoimmunity. Here, using a double transgenic mouse model that permits Foxp3 lineage tracing, we investigated the phenotypic plasticity of Foxp3+ Tregs in a well-characterized murine model of corneal transplantation. In order to subvert the normal immune privilege of the cornea and foster an inflammatory milieu, host mice were exposed to desiccating stress prior to transplantation...
May 4, 2018: Scientific Reports
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