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Effects of NRP1 on angiogenesis and vascular maturity in endothelial cells are dependent on the expression of SEMA4D

Angiogenesis and vascular maturation play important roles in tumorigenesis and tumor development. The expression of neuropilin 1 (NRP1) is closely associated with angiogenesis in tumors; however, the molecular mechanisms of action in angiogenesis and tumor maturation, as well as the potential clinic...

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Autores principales: Lyu, Zhi, Jin, Hongwei, Yan, Zhijian, Hu, Keyan, Jiang, Hongwei, Peng, Huifang, Zhuo, Huiqin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447310/
https://www.ncbi.nlm.nih.gov/pubmed/32945351
http://dx.doi.org/10.3892/ijmm.2020.4692
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author Lyu, Zhi
Jin, Hongwei
Yan, Zhijian
Hu, Keyan
Jiang, Hongwei
Peng, Huifang
Zhuo, Huiqin
author_facet Lyu, Zhi
Jin, Hongwei
Yan, Zhijian
Hu, Keyan
Jiang, Hongwei
Peng, Huifang
Zhuo, Huiqin
author_sort Lyu, Zhi
collection PubMed
description Angiogenesis and vascular maturation play important roles in tumorigenesis and tumor development. The expression of neuropilin 1 (NRP1) is closely associated with angiogenesis in tumors; however, the molecular mechanisms of action in angiogenesis and tumor maturation, as well as the potential clinical value of NRP1 remain unclear. The importance of NRP1 expression in tumor progression was determined using The Cancer Genome Atlas (TCGA) database analysis. Gain- and loss-of-function experiments of NRP1 were performed in vascular endothelial cells (ECs) to investigate the functions in angiogenesis. CCK-8, flow cytometry, Transwell experiments and a series of in vitro experiments were used to detect cell functions. A combination of angiogenesis antibody arrays and RNA-Seq analyses were performed to reveal the proangiogenic mechanisms of action. The function of semaphorin 4D (SEMA4D) was also investigated separately. NRP1 mRNA levels were significantly increased in primary tumors compared with normal tissues based on TCGA data (P<0.01) and were associated with tumor development in patients. Gain- and loss-of-function experiments highlighted the function of NRP1 in promoting EC proliferation, motility and capillary-like tube formation and in reducing apoptosis. NRP1 overexpression led to significantly decreased EC markers (PECAM-1, angiogenin, PIGF and MMP-9) expression levels and reduced the vascular maturity. MAPK7, TPM1, RRBP1, PTPRK, HSP90A, PRKD2, PFKFB3, RGS4 and SPARC were revealed to play important roles in this process. SEMA4D was revealed to be a key protein associated with NRP1 in ECs. These data indicated that NRP1-promoted angiogenesis may be induced at the cost of reducing maturity of the ECs. NRP1 may also be a therapeutic target for antiangiogenic strategies and a candidate prognostic marker for tumors.
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spelling pubmed-74473102020-08-28 Effects of NRP1 on angiogenesis and vascular maturity in endothelial cells are dependent on the expression of SEMA4D Lyu, Zhi Jin, Hongwei Yan, Zhijian Hu, Keyan Jiang, Hongwei Peng, Huifang Zhuo, Huiqin Int J Mol Med Articles Angiogenesis and vascular maturation play important roles in tumorigenesis and tumor development. The expression of neuropilin 1 (NRP1) is closely associated with angiogenesis in tumors; however, the molecular mechanisms of action in angiogenesis and tumor maturation, as well as the potential clinical value of NRP1 remain unclear. The importance of NRP1 expression in tumor progression was determined using The Cancer Genome Atlas (TCGA) database analysis. Gain- and loss-of-function experiments of NRP1 were performed in vascular endothelial cells (ECs) to investigate the functions in angiogenesis. CCK-8, flow cytometry, Transwell experiments and a series of in vitro experiments were used to detect cell functions. A combination of angiogenesis antibody arrays and RNA-Seq analyses were performed to reveal the proangiogenic mechanisms of action. The function of semaphorin 4D (SEMA4D) was also investigated separately. NRP1 mRNA levels were significantly increased in primary tumors compared with normal tissues based on TCGA data (P<0.01) and were associated with tumor development in patients. Gain- and loss-of-function experiments highlighted the function of NRP1 in promoting EC proliferation, motility and capillary-like tube formation and in reducing apoptosis. NRP1 overexpression led to significantly decreased EC markers (PECAM-1, angiogenin, PIGF and MMP-9) expression levels and reduced the vascular maturity. MAPK7, TPM1, RRBP1, PTPRK, HSP90A, PRKD2, PFKFB3, RGS4 and SPARC were revealed to play important roles in this process. SEMA4D was revealed to be a key protein associated with NRP1 in ECs. These data indicated that NRP1-promoted angiogenesis may be induced at the cost of reducing maturity of the ECs. NRP1 may also be a therapeutic target for antiangiogenic strategies and a candidate prognostic marker for tumors. D.A. Spandidos 2020-10 2020-08-03 /pmc/articles/PMC7447310/ /pubmed/32945351 http://dx.doi.org/10.3892/ijmm.2020.4692 Text en Copyright: © Lyu et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Lyu, Zhi
Jin, Hongwei
Yan, Zhijian
Hu, Keyan
Jiang, Hongwei
Peng, Huifang
Zhuo, Huiqin
Effects of NRP1 on angiogenesis and vascular maturity in endothelial cells are dependent on the expression of SEMA4D
title Effects of NRP1 on angiogenesis and vascular maturity in endothelial cells are dependent on the expression of SEMA4D
title_full Effects of NRP1 on angiogenesis and vascular maturity in endothelial cells are dependent on the expression of SEMA4D
title_fullStr Effects of NRP1 on angiogenesis and vascular maturity in endothelial cells are dependent on the expression of SEMA4D
title_full_unstemmed Effects of NRP1 on angiogenesis and vascular maturity in endothelial cells are dependent on the expression of SEMA4D
title_short Effects of NRP1 on angiogenesis and vascular maturity in endothelial cells are dependent on the expression of SEMA4D
title_sort effects of nrp1 on angiogenesis and vascular maturity in endothelial cells are dependent on the expression of sema4d
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447310/
https://www.ncbi.nlm.nih.gov/pubmed/32945351
http://dx.doi.org/10.3892/ijmm.2020.4692
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