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Inhibition of FABP6 Reduces Tumor Cell Invasion and Angiogenesis through the Decrease in MMP-2 and VEGF in Human Glioblastoma Cells

Malignant glioma is one of the most lethal cancers with rapid progression, high recurrence, and poor prognosis in the central nervous system. Fatty acid-binding protein 6 (FABP6) is a bile acid carrier protein that is overexpressed in colorectal cancer. This study aimed to assess the involvement of...

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Autores principales: Pai, Feng-Cheng, Huang, Hsiang-Wei, Tsai, Yu-Ling, Tsai, Wen-Chiuan, Cheng, Yu-Chen, Chang, Hsin-Han, Chen, Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534568/
https://www.ncbi.nlm.nih.gov/pubmed/34685761
http://dx.doi.org/10.3390/cells10102782
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author Pai, Feng-Cheng
Huang, Hsiang-Wei
Tsai, Yu-Ling
Tsai, Wen-Chiuan
Cheng, Yu-Chen
Chang, Hsin-Han
Chen, Ying
author_facet Pai, Feng-Cheng
Huang, Hsiang-Wei
Tsai, Yu-Ling
Tsai, Wen-Chiuan
Cheng, Yu-Chen
Chang, Hsin-Han
Chen, Ying
author_sort Pai, Feng-Cheng
collection PubMed
description Malignant glioma is one of the most lethal cancers with rapid progression, high recurrence, and poor prognosis in the central nervous system. Fatty acid-binding protein 6 (FABP6) is a bile acid carrier protein that is overexpressed in colorectal cancer. This study aimed to assess the involvement of FABP6 expression in the progression of malignant glioma. Immunohistochemical analysis revealed that FABP6 expression was higher in glioma than in normal brain tissue. After the knockdown of FABP6, a decrease in the migration and invasion abilities of glioma cells was observed. The phosphorylation of the myosin light chain was inhibited, which may be associated with migration ability. Moreover, expression levels of invasion-related proteins, matrix metalloproteinase-2 (MMP-2) and cathepsin B, were reduced. Furthermore, tube formation was inhibited in the human umbilical vein endothelial cells with a decreased concentration of vascular endothelial growth factor (VEGF) in the conditioned medium after the knockdown of FABP6. The phosphorylation of the extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p65 were also decreased after FABP6 reduction. Finally, the bioluminescent images and immunostaining of MMP-2, cluster of differentiation 31 (CD31), and the VEGF receptor 1 (VEGFR1) revealed attenuated tumor progression in the combination of the FABP6-knocked-down and temozolomide (TMZ)-treated group in an orthotopic xenograft mouse tumor model. This is the first study that revealed the impact of FABP6 on the invasion, angiogenesis, and progression of glioma. The results of this study show that FABP6 may be a potential therapeutic target combined with TMZ for malignant gliomas.
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spelling pubmed-85345682021-10-23 Inhibition of FABP6 Reduces Tumor Cell Invasion and Angiogenesis through the Decrease in MMP-2 and VEGF in Human Glioblastoma Cells Pai, Feng-Cheng Huang, Hsiang-Wei Tsai, Yu-Ling Tsai, Wen-Chiuan Cheng, Yu-Chen Chang, Hsin-Han Chen, Ying Cells Article Malignant glioma is one of the most lethal cancers with rapid progression, high recurrence, and poor prognosis in the central nervous system. Fatty acid-binding protein 6 (FABP6) is a bile acid carrier protein that is overexpressed in colorectal cancer. This study aimed to assess the involvement of FABP6 expression in the progression of malignant glioma. Immunohistochemical analysis revealed that FABP6 expression was higher in glioma than in normal brain tissue. After the knockdown of FABP6, a decrease in the migration and invasion abilities of glioma cells was observed. The phosphorylation of the myosin light chain was inhibited, which may be associated with migration ability. Moreover, expression levels of invasion-related proteins, matrix metalloproteinase-2 (MMP-2) and cathepsin B, were reduced. Furthermore, tube formation was inhibited in the human umbilical vein endothelial cells with a decreased concentration of vascular endothelial growth factor (VEGF) in the conditioned medium after the knockdown of FABP6. The phosphorylation of the extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p65 were also decreased after FABP6 reduction. Finally, the bioluminescent images and immunostaining of MMP-2, cluster of differentiation 31 (CD31), and the VEGF receptor 1 (VEGFR1) revealed attenuated tumor progression in the combination of the FABP6-knocked-down and temozolomide (TMZ)-treated group in an orthotopic xenograft mouse tumor model. This is the first study that revealed the impact of FABP6 on the invasion, angiogenesis, and progression of glioma. The results of this study show that FABP6 may be a potential therapeutic target combined with TMZ for malignant gliomas. MDPI 2021-10-17 /pmc/articles/PMC8534568/ /pubmed/34685761 http://dx.doi.org/10.3390/cells10102782 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pai, Feng-Cheng
Huang, Hsiang-Wei
Tsai, Yu-Ling
Tsai, Wen-Chiuan
Cheng, Yu-Chen
Chang, Hsin-Han
Chen, Ying
Inhibition of FABP6 Reduces Tumor Cell Invasion and Angiogenesis through the Decrease in MMP-2 and VEGF in Human Glioblastoma Cells
title Inhibition of FABP6 Reduces Tumor Cell Invasion and Angiogenesis through the Decrease in MMP-2 and VEGF in Human Glioblastoma Cells
title_full Inhibition of FABP6 Reduces Tumor Cell Invasion and Angiogenesis through the Decrease in MMP-2 and VEGF in Human Glioblastoma Cells
title_fullStr Inhibition of FABP6 Reduces Tumor Cell Invasion and Angiogenesis through the Decrease in MMP-2 and VEGF in Human Glioblastoma Cells
title_full_unstemmed Inhibition of FABP6 Reduces Tumor Cell Invasion and Angiogenesis through the Decrease in MMP-2 and VEGF in Human Glioblastoma Cells
title_short Inhibition of FABP6 Reduces Tumor Cell Invasion and Angiogenesis through the Decrease in MMP-2 and VEGF in Human Glioblastoma Cells
title_sort inhibition of fabp6 reduces tumor cell invasion and angiogenesis through the decrease in mmp-2 and vegf in human glioblastoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534568/
https://www.ncbi.nlm.nih.gov/pubmed/34685761
http://dx.doi.org/10.3390/cells10102782
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