Correlation of Matrisome-Associatted Gene Expressions with LOX Family Members in Astrocytomas Stratified by IDH Mutation Status
Tumor cell infiltrative ability into surrounding brain tissue is a characteristic of diffusely infiltrative astrocytoma and is strongly associated with extracellular matrix (ECM) stiffness. Collagens are the most abundant ECM scaffolding proteins and contribute to matrix organization and stiffness....
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MDPI AG
2022-08-01
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author | Talita de Sousa Laurentino Roseli da Silva Soares Suely Kazue Nagahashi Marie Sueli Mieko Oba-Shinjo |
author_facet | Talita de Sousa Laurentino Roseli da Silva Soares Suely Kazue Nagahashi Marie Sueli Mieko Oba-Shinjo |
author_sort | Talita de Sousa Laurentino |
collection | DOAJ |
description | Tumor cell infiltrative ability into surrounding brain tissue is a characteristic of diffusely infiltrative astrocytoma and is strongly associated with extracellular matrix (ECM) stiffness. Collagens are the most abundant ECM scaffolding proteins and contribute to matrix organization and stiffness. LOX family members, copper-dependent amine oxidases, participate in the collagen and elastin crosslinking that determine ECM tensile strength. Common IDH mutations in lower-grade gliomas (LGG) impact prognosis and have been associated with ECM stiffness. We analyzed the expression levels of LOX family members and matrisome-associated genes in astrocytoma stratified by malignancy grade and IDH mutation status. A progressive increase in expression of all five LOX family members according to malignancy grade was found. <i>LOX</i>, <i>LOXL1</i>, and <i>LOXL3</i> expression correlated with matrisome gene expressions. LOXL1 correlations were detected in LGG with <i>IDH</i> mutation (IDH<sup>mut</sup>), <i>LOXL3</i> correlations in LGG with IDH wild type (IDH<sup>wt</sup>) and strong <i>LOX</i> correlations in glioblastoma (GBM) were found. These increasing correlations may explain the increment of ECM stiffness and tumor aggressiveness from LGG-IDH<sup>mut</sup> and LGG-IDH<sup>wt</sup> through to GBM. The expression of the mechanosensitive transcription factor, β-catenin, also increased with malignancy grade and was correlated with <i>LOXL1</i> and LOXL3 expression, suggesting involvement of this factor in the outside–in signaling pathway. |
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spelling | doaj.art-c2358cf3204b48fa8917db62975233812023-11-23T13:11:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012317950710.3390/ijms23179507Correlation of Matrisome-Associatted Gene Expressions with LOX Family Members in Astrocytomas Stratified by IDH Mutation StatusTalita de Sousa Laurentino0Roseli da Silva Soares1Suely Kazue Nagahashi Marie2Sueli Mieko Oba-Shinjo3Cellular and Molecular Biology Laboratory (LIM 15), Neurology Department, Faculdade de Medicina (FMUSP), Universidade de Sao Paulo, Sao Paulo 01246-903, SP, BrazilCellular and Molecular Biology Laboratory (LIM 15), Neurology Department, Faculdade de Medicina (FMUSP), Universidade de Sao Paulo, Sao Paulo 01246-903, SP, BrazilCellular and Molecular Biology Laboratory (LIM 15), Neurology Department, Faculdade de Medicina (FMUSP), Universidade de Sao Paulo, Sao Paulo 01246-903, SP, BrazilCellular and Molecular Biology Laboratory (LIM 15), Neurology Department, Faculdade de Medicina (FMUSP), Universidade de Sao Paulo, Sao Paulo 01246-903, SP, BrazilTumor cell infiltrative ability into surrounding brain tissue is a characteristic of diffusely infiltrative astrocytoma and is strongly associated with extracellular matrix (ECM) stiffness. Collagens are the most abundant ECM scaffolding proteins and contribute to matrix organization and stiffness. LOX family members, copper-dependent amine oxidases, participate in the collagen and elastin crosslinking that determine ECM tensile strength. Common IDH mutations in lower-grade gliomas (LGG) impact prognosis and have been associated with ECM stiffness. We analyzed the expression levels of LOX family members and matrisome-associated genes in astrocytoma stratified by malignancy grade and IDH mutation status. A progressive increase in expression of all five LOX family members according to malignancy grade was found. <i>LOX</i>, <i>LOXL1</i>, and <i>LOXL3</i> expression correlated with matrisome gene expressions. LOXL1 correlations were detected in LGG with <i>IDH</i> mutation (IDH<sup>mut</sup>), <i>LOXL3</i> correlations in LGG with IDH wild type (IDH<sup>wt</sup>) and strong <i>LOX</i> correlations in glioblastoma (GBM) were found. These increasing correlations may explain the increment of ECM stiffness and tumor aggressiveness from LGG-IDH<sup>mut</sup> and LGG-IDH<sup>wt</sup> through to GBM. The expression of the mechanosensitive transcription factor, β-catenin, also increased with malignancy grade and was correlated with <i>LOXL1</i> and LOXL3 expression, suggesting involvement of this factor in the outside–in signaling pathway.https://www.mdpi.com/1422-0067/23/17/9507lysyl oxidasematrisomeglioblastomadiffuse astrocyticprogressionLOX |
spellingShingle | Talita de Sousa Laurentino Roseli da Silva Soares Suely Kazue Nagahashi Marie Sueli Mieko Oba-Shinjo Correlation of Matrisome-Associatted Gene Expressions with LOX Family Members in Astrocytomas Stratified by IDH Mutation Status International Journal of Molecular Sciences lysyl oxidase matrisome glioblastoma diffuse astrocytic progression LOX |
title | Correlation of Matrisome-Associatted Gene Expressions with LOX Family Members in Astrocytomas Stratified by IDH Mutation Status |
title_full | Correlation of Matrisome-Associatted Gene Expressions with LOX Family Members in Astrocytomas Stratified by IDH Mutation Status |
title_fullStr | Correlation of Matrisome-Associatted Gene Expressions with LOX Family Members in Astrocytomas Stratified by IDH Mutation Status |
title_full_unstemmed | Correlation of Matrisome-Associatted Gene Expressions with LOX Family Members in Astrocytomas Stratified by IDH Mutation Status |
title_short | Correlation of Matrisome-Associatted Gene Expressions with LOX Family Members in Astrocytomas Stratified by IDH Mutation Status |
title_sort | correlation of matrisome associatted gene expressions with lox family members in astrocytomas stratified by idh mutation status |
topic | lysyl oxidase matrisome glioblastoma diffuse astrocytic progression LOX |
url | https://www.mdpi.com/1422-0067/23/17/9507 |
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