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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Main Authors: Talita de Sousa Laurentino, Roseli da Silva Soares, Suely Kazue Nagahashi Marie, Sueli Mieko Oba-Shinjo
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/17/9507
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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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AT suelykazuenagahashimarie correlationofmatrisomeassociattedgeneexpressionswithloxfamilymembersinastrocytomasstratifiedbyidhmutationstatus
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