GFAPδ: A Promising Biomarker and Therapeutic Target in Glioblastoma

Radu, Roxana A.; Petrescu, G; Gorgan, R.M.; Brehar, Felix Mircea

doi:10.3389/fonc.2022.859247

Cited by 14 publications

(10 citation statements)

References 75 publications

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“…Of note, VEGF-A had the greatest increase in signal of all aptamers elevated with progression through bevacizumab (14.45x), consistent with its relevance to blood-brain barrier disruption in HGGs( 45, 46 ) in the setting of failed radiographic response to this anti-VEGF-A antibody ( Figure 4A) . GFAP was also evaluated as a previously proposed biomarker of GBM( 47–49 ) and one of the top proteins that increased with progression through bevacizumab (3.59x). However, unlike BCAN, both VEGF-A and GFAP did not increase with progression through lomustine (1.03x and 0.63x, respectively).…”

Section: Resultsmentioning

confidence: 99%

The dynamic impact of location and resection on the glioma CSF proteome

Riviere-Cazaux,

Graser,

Warrington

et al. 2024

Preprint

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While serial sampling of glioma tissue is rarely performed prior to recurrence, cerebrospinal fluid (CSF) is an underutilized longitudinal source of candidate glioma biomarkers for understanding therapeutic impacts. However, the impact of key variables to consider in longitudinal CSF samples, including anatomical location and post-surgical changes, remains unknown. To that end, pre- versus post-resection intracranial CSF samples were obtained at early (1-16 days; n=20) or delayed (86-153 days; n=11) timepoints for patients with glioma. Paired lumbar-versus-intracranial glioma CSF samples were also obtained (n=14). Using aptamer-based proteomics, we identify significant differences in the CSF proteome between lumbar, subarachnoid, and ventricular CSF. Our analysis of serial intracranial CSF samples suggests the early potential for disease monitoring and evaluation of pharmacodynamic impact of targeted therapies. Importantly, we found that resection had a significant, evolving longitudinal impact on the CSF proteome. Proteomic data are provided with individual clinical annotations as a resource for the field.

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Section: Resultsmentioning

confidence: 99%

The dynamic impact of location and resection on the glioma CSF proteome

Riviere-Cazaux,

Graser,

Warrington

et al. 2024

Preprint

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“…GFAP overexpression in GBM is frequently associated with blood–brain barrier disruption, and it is commonly found in patients’ serum as a biomarker for gliomas ( Yadav et al, 2022 ; Ghorbani et al, 2023 ). Alternative GFAP isoforms produced by alternative splicing have recently attracted attention for biomarker identification ( Radu et al, 2022 ). It has been shown that GFAP splice variant isoform ratios modulate glioma cell invasion, cytoskeleton dynamic, and organization ( Moeton et al, 2016 ; Stassen et al, 2017 ; van Bodegraven et al, 2019c ; Uceda-Castro et al, 2022 ; van Asperen et al, 2022 ), suggesting that GFAP is not only a passive viewer in GBM but could also play an active role and highlight the correlation between GFAP and cytoskeleton remodeling in GBM cells.…”

Section: Discussionmentioning

confidence: 99%

GFAP serves as a structural element of tunneling nanotubes between glioblastoma cells and could play a role in the intercellular transfer of mitochondria

Simone,

Capobianco,

Di Palma

et al. 2023

Front. Cell Dev. Biol.

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Tunneling nanotubes (TNTs) are long F-actin-positive plasma membrane bridges connecting distant cells, allowing the intercellular transfer of cellular cargoes, and are found to be involved in glioblastoma (GBM) intercellular crosstalk. Glial fibrillary acid protein (GFAP) is a key intermediate filament protein of glial cells involved in cytoskeleton remodeling and linked to GBM progression. Whether GFAP plays a role in TNT structure and function in GBM is unknown. Here, analyzing F-actin and GFAP localization by laser-scan confocal microscopy followed by 3D reconstruction (3D-LSCM) and mitochondria dynamic by live-cell time-lapse fluorescence microscopy, we show the presence of GFAP in TNTs containing functional mitochondria connecting distant human GBM cells. Taking advantage of super-resolution 3D-LSCM, we show the presence of GFAP-positive TNT-like structures in resected human GBM as well. Using H2O2 or the pro-apoptotic toxin staurosporine (STS), we show that GFAP-positive TNTs strongly increase during oxidative stress and apoptosis in the GBM cell line. Culturing GBM cells with STS-treated GBM cells, we show that STS triggers the formation of GFAP-positive TNTs between them. Finally, we provide evidence that mitochondria co-localize with GFAP at the tip of close-ended GFAP-positive TNTs and inside receiving STS-GBM cells. Summarizing, here we found that GFAP is a structural component of TNTs generated by GBM cells, that GFAP-positive TNTs are upregulated in response to oxidative stress and pro-apoptotic stress, and that GFAP interacts with mitochondria during the intercellular transfer. These findings contribute to elucidate the molecular structure of TNTs generated by GBM cells, highlighting the structural role of GFAP in TNTs and suggesting a functional role of this intermediate filament component in the intercellular mitochondria transfer between GBM cells in response to pro-apoptotic stimuli.

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“…GFAP is a glial fibrillary acidic protein that is a promising biomarker and therapeutic target in glioblastoma ( 69 ) and other cancers ( 70 , 71 ); however, its role in prostate cancer has not been fully explored. One of the bioinformatics investigations nominated GFAP as a potential regulator of immune phenotypes in prostate cancer ( 72 ), yet its role in prostate cancer progression provides a new exciting avenue for further investigation, especially in combination with GADD45B, STAT3, and GFAP (and, potentially, FOXM1).…”

Section: Discussionmentioning

confidence: 99%

Tissue-specific biological aging predicts progression in prostate cancer and acute myeloid leukemia

Ramakrishnan,

Datta,

Panja

et al. 2023

Front. Oncol.

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IntroductionChronological aging is a well-recognized diagnostic and prognostic factor in multiple cancer types, yet the role of biological aging in manifesting cancer progression has not been fully explored yet.MethodsGiven the central role of chronological aging in prostate cancer and AML incidence, here we investigate a tissue-specific role of biological aging in prostate cancer and AML progression. We have employed Cox proportional hazards modeling to associate biological aging genes with cancer progression for patients from specific chronological aging groups and for patients with differences in initial cancer aggressiveness.ResultsOur prostate cancer-specific investigations nominated four biological aging genes (CD44, GADD45B, STAT3, GFAP) significantly associated with time to disease progression in prostate cancer in Taylor et al. patient cohort. Stratified survival analysis on Taylor dataset and validation on an independent TCGA and DKFZ PRAD patient cohorts demonstrated ability of these genes to predict prostate cancer progression, especially for patients with higher Gleason score and for patients younger than 60 years of age. We have further tested the generalizability of our approach and applied it to acute myeloid leukemia (AML). Our analysis nominated three AML-specific biological aging genes (CDC42EP2, CDC42, ALOX15B) significantly associated with time to AML overall survival, especially for patients with favorable cytogenetic risk score and for patients older than 56 years of age.DiscussionComparison of the identified PC and AML markers to genes selected at random and to known markers of progression demonstrated robustness of our results and nominated the identified biological aging genes as valuable markers of prostate cancer and AML progression, opening new avenues for personalized therapeutic management and potential novel treatment investigations.

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GFAPδ: A Promising Biomarker and Therapeutic Target in Glioblastoma

Cited by 14 publications

References 75 publications

The dynamic impact of location and resection on the glioma CSF proteome

The dynamic impact of location and resection on the glioma CSF proteome

GFAP serves as a structural element of tunneling nanotubes between glioblastoma cells and could play a role in the intercellular transfer of mitochondria

Tissue-specific biological aging predicts progression in prostate cancer and acute myeloid leukemia

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