Expression of lumican and osteopontin in perivascular areas of the glioblastoma peritumoral niche and its value for prognosis

Rodríguez, Pablo; Rubio Pedraza, Gonzalo; Salinas Hidalgo, María Dolores; Valdor Alonso, Rut

Publication:
Expression of lumican and osteopontin in perivascular areas of the glioblastoma peritumoral niche and its value for prognosis

dc.contributor.author	Rodríguez, Pablo
dc.contributor.author	Rubio Pedraza, Gonzalo
dc.contributor.author	Salinas Hidalgo, María Dolores
dc.contributor.author	Valdor Alonso, Rut
dc.contributor.department	Bioquímica y Biología Molecular B e Inmunología	es
dc.date.accessioned	2025-09-03T07:39:16Z
dc.date.available	2025-09-03T07:39:16Z
dc.date.issued	2024-12-29
dc.description	© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/. This document is the Published version of a Published Work that appeared in final form in International Journal of Molecular Sciences. To access the final edited and published work see https://doi.org/10.3390/ijms26010192
dc.description.abstract	Glioblastoma (GB) is one of the most aggressive and treatment-resistant cancers due to its complex tumor microenvironment (TME). We previously showed that GB progression is dependent on the aberrant induction of chaperone-mediated autophagy (CMA) in pericytes (PCs), which promotes TME immunosuppression through the PC secretome. The secretion of extracellular matrix (ECM) proteins with anti-tumor (Lumican) and pro-tumoral (Osteopontin, OPN) properties was shown to be dependent on the regulation of GB-induced CMA in PCs. As biomarkers are rarely studied in TME, in this work, we aimed to validate Lumican and OPN as prognostic markers in the perivascular areas of the peritumoral niche of a cohort of GB patients. Previously, we had validated their expression in GB xenografted mice presenting GB infiltration (OPN) or GB elimination (Lumican) dependent on competent or deficient CMA PCs, respectively. Then, patient sample classification by GB infiltration into the peritumoral brain parenchyma was related to GB-induced CMA in microvasculature PCs, analyzing the expression of the lysosomal receptor, LAMP-2A. Our results revealed a correlation between GB-induced CMA activity in peritumoral PCs and GB patients’ outcomes, identifying three degrees of severity. The perivascular expression of both immune activation markers, Iba1 and CD68, was related to CMA-dependent PC immune function and determined as useful for efficient GB prognosis. Lumican expression was identified in perivascular areas of patients with less severe outcome and partially co-localizing with PCs presenting low CMA activity, while OPN was primarily found in perivascular areas of patients with poor outcome and partially co-localizing with PCs presenting high CMA activity. Importantly, we found sex differences in the incidence of middle-aged patients, being significantly higher in men but with worse prognosis in women. Our results confirmed that Lumican and OPN in perivascular areas of the GB peritumoral niche are effective predictive biomarkers for evaluating prognosis and monitoring possible therapeutic immune responses dependent on PCs in tumor progression.	es
dc.format	application/pdf	es
dc.identifier.citation	Int. J. Mol. Sci. 2025, 26, 192.
dc.identifier.doi	https://doi.org/10.3390/ijms26010192
dc.identifier.uri	http://hdl.handle.net/10201/158066
dc.language	eng	es
dc.publisher	MDPI
dc.relation	This work was developed by Ramon y Cajal (RYC) 2019-027520-I funded by Ministerio de Ciencia e Innovación (MCIN) and Agencia Estatal de Investigación (AEI) MCIN/AEI/10.13039/501100011033, as “ESF Investing in your future” and by PID2020-114010RB-I00 funded by MCIN/AEI/10.13039/501100011033 (to RV). It was also partially supported by Seneca 22239/PDC23 funded by Seneca Foundation “Agencia de Ciencia y Tecnología de la Región de Murcia” (to RV).	es
dc.relation.publisherversion	https://www.mdpi.com/1422-0067/26/1/192	es
dc.rights	info:eu-repo/semantics/openAccess	es
dc.rights	Atribución 4.0 Internacional	*
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/	*
dc.subject	Glioblastoma	es
dc.subject	Tumor microenvironment	es
dc.subject	Pericyte	es
dc.subject	Perivascular	es
dc.subject	Peritumoral	es
dc.subject	Biomarker	es
dc.subject	Sex differences	es
dc.subject	CD68	es
dc.subject	Iba-1	es
dc.subject	Chaperone-mediated autophagy	es
dc.subject	LAMP-2A	es
dc.subject	Lumican	es
dc.subject	Osteopontin	es
dc.title	Expression of lumican and osteopontin in perivascular areas of the glioblastoma peritumoral niche and its value for prognosis	es
dc.type	info:eu-repo/semantics/article	es
dspace.entity.type	Publication	es
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