Browsing by Subject "Peritumoral"

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    Dataset of the project: Una Posible Diana Terapeutica para Bloquear la Progresión del Glioblastoma: la Autofagia Mediada por Chaperonas en Pericitos (PID2020-114010RB-I00)
    (2026-02-09) Rodríguez, Pablo; Rubio Pedraza, Gonzalo; Valdor Alonso, Rut; Salinas Hidalgo, María Dolores; Bioquímica y Biología Molecular B e Inmunología
    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
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    Expression of lumican and osteopontin in perivascular areas of the glioblastoma peritumoral niche and its value for prognosis
    (MDPI, 2024-12-29) Rodríguez, Pablo; Rubio Pedraza, Gonzalo; Salinas Hidalgo, María Dolores; Valdor Alonso, Rut; Bioquímica y Biología Molecular B e Inmunología
    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.
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    The effect of Glioblastoma on Pericytes
    (2020-10-29) Molina Gallego, María Luisa; Valdor Alonso, Rut; Bioquímica y Biología Molecular B e Inmunología
    Purpose of the Review: Intratumoral pericytes (PC) do not share the same tumor niche as peritumoral PC. Furthermore, glioblastoma multiforme (GB) cells do not seem to affect them equally. Therefore, for a better understanding of the effects of GB on PC, in this chapter, we will classify them according to whether they are intratumoral or peritumoral PC, focusing mainly on peritumoral effects, which seem to have better future prospects for finding effective therapies in GB cancer. Recent Findings: Recently, it has been shown that PC could be the main target of the tumor infiltration front and have a fundamental role in the proliferation, expansion, and survival of the tumor, as well as in the regulation of anti-tumor immune responses. Modulation of the immune function of PC through molecular mechanisms such as chaperone-mediated autophagy (CMA) seems to be essential to prevent an immunosuppressive microenviroment that facilitates tumor growth. Summary: GB is the most frequent and aggressive brain tumor. In the last years, PC have been gaining special attention due to their role in GB progression. GB cells infiltrate away from the tumor core more often and faster when they are associated with perivascular cells. However, to find targeted therapies against PC to promote their brain defense function and improve anti-tumor immune responses requires a better understanding of the heterogeneity, markers, and distribution of PC at origin.