New Cellular Dimensions on Glioblastoma Progression

Portela, Marta; Casas‐Tintó, Sergio

doi:10.1177/2633105520923076

Cited by 8 publications

(5 citation statements)

References 22 publications

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“…By blocking L-type voltage-gated Ca 2+ channels, cell invasion is inhibited as filopodia (also known as tumor microtubes, TMs) formation is blocked [ 140 ]. Indeed, GB cells possess the ability to extract specific signals from healthy neurons using TMs [ 141 ]. Furthermore, inhibition of T-type Ca 2+ channels has been shown to induce apoptosis in GB cells [ 142 ].…”

Section: Lessons Learned In the Pathophysiology Of Glioblastomamentioning

confidence: 99%

Glioblastoma Therapy: Past, Present and Future

Obrador,

Moreno-Murciano,

Oriol-Caballo

et al. 2024

IJMS

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Glioblastoma (GB) stands out as the most prevalent and lethal form of brain cancer. Although great efforts have been made by clinicians and researchers, no significant improvement in survival has been achieved since the Stupp protocol became the standard of care (SOC) in 2005. Despite multimodality treatments, recurrence is almost universal with survival rates under 2 years after diagnosis. Here, we discuss the recent progress in our understanding of GB pathophysiology, in particular, the importance of glioma stem cells (GSCs), the tumor microenvironment conditions, and epigenetic mechanisms involved in GB growth, aggressiveness and recurrence. The discussion on therapeutic strategies first covers the SOC treatment and targeted therapies that have been shown to interfere with different signaling pathways (pRB/CDK4/RB1/P16ink4, TP53/MDM2/P14arf, PI3k/Akt-PTEN, RAS/RAF/MEK, PARP) involved in GB tumorigenesis, pathophysiology, and treatment resistance acquisition. Below, we analyze several immunotherapeutic approaches (i.e., checkpoint inhibitors, vaccines, CAR-modified NK or T cells, oncolytic virotherapy) that have been used in an attempt to enhance the immune response against GB, and thereby avoid recidivism or increase survival of GB patients. Finally, we present treatment attempts made using nanotherapies (nanometric structures having active anti-GB agents such as antibodies, chemotherapeutic/anti-angiogenic drugs or sensitizers, radionuclides, and molecules that target GB cellular receptors or open the blood–brain barrier) and non-ionizing energies (laser interstitial thermal therapy, high/low intensity focused ultrasounds, photodynamic/sonodynamic therapies and electroporation). The aim of this review is to discuss the advances and limitations of the current therapies and to present novel approaches that are under development or following clinical trials.

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Section: Lessons Learned In the Pathophysiology Of Glioblastomamentioning

confidence: 99%

Glioblastoma Therapy: Past, Present and Future

Obrador,

Moreno-Murciano,

Oriol-Caballo

et al. 2024

IJMS

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“…The EGF pathway is often found cooperating with signals such as the Phosphatidylinositol 3-Kinase (PI3K) (Portela and Casas-Tintó, 2020). Thus, we next checked whether this role of EGF activity as regulator of Hh-cytoneme dynamics could also be influenced by PI3K.…”

Section: Egf and Pi3k Signals Have A Synergic Effect Over Hh Cytonemesmentioning

confidence: 99%

The Drosophila Epidermal growth factor regulates Hedgehog-signalling cytoneme dynamics.

Gradilla

Sánchez‐Hernández

Jiménez-Jiménez

et al. 2023

Preprint

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During Drosophila epithelial development, signalling specialized filopodial or cytonemes establish direct contacts between distant cells to facilitate the formation of the Hedgehog (Hh) signalling gradient. However, the regulatory mechanisms for Hh cytoneme initiation and their dynamic behaviour are still unknown. Here we show that Hh cytoneme dynamics in Drosophila epithelia depends on the Epidermal Growth Factor (EGF) signalling pathway through its ligand Spitz. We describe that the EGF pathway is required to maintain basal plasma membrane levels of the adhesion protein and Hh co-receptor Ihog, able to modify cyoneme behaviour. Furthermore, we describe that EGF signalling promotes Ihog interaction with actin cytoskeleton regulators, such as the actin cross-linker Filamin A, Cheerio (Che) in Drosophila. Cheerio is recruited by Ihog towards focalized small regions of the plasma membrane to contribute to the cytoneme stabilization function of Ihog. Finally, we describe that EGF regulation and PI3K signalling act synergically on Hh cytoneme behaviour, revealing a new form of cooperation between major tissue organizers.

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“…The U251 cells also feature the presence of minor (Figure 3A, A1 arrow) and major (Figure 3A, A3 arrow) extensions which are filopodia-like membrane protrusions, that assist the cell in maneuvering, navigating, and invading its microenvironment. [53,55] The terms major and minor extensions were chosen here to distinguish between two main protrusion groups according to their physical characteristics as observed in the SEM micrographs. The major extensions have a diameter of 1-1.5 μm, while the minor extensions feature a "hair-like" appearance with diameters of 0.3-0.5 μm.…”

Section: Sem and 3d Immunofluorescence Characterization Of The U251 A...mentioning

confidence: 99%

Micro‐Vessels‐Like 3D Scaffolds for Studying the Proton Radiobiology of Glioblastoma‐Endothelial Cells Co‐Culture Models

Akolawala,

Keuning,

Rovituso

et al. 2023

Adv Healthcare Materials

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Glioblastoma (GBM) is a devastating cancer of the brain with an extremely poor prognosis. While X‐ray radiotherapy and chemotherapy remain the current standard, proton beam therapy is an appealing alternative as protons can damage cancer cells while sparing the surrounding healthy tissue. However, the effects of protons on in vitro GBM models at the cellular level, especially when co‐cultured with endothelial cells, the building blocks of brain micro‐vessels, are still unexplored. In this work, novel 3D‐engineered scaffolds inspired by the geometry of brain microvasculature are designed, where GBM cells cluster and proliferate. The architectures are fabricated by two‐photon polymerization (2PP), pre‐cultured with endothelial cells (HUVECs), and then cultured with a human GBM cell line (U251). The micro‐vessel structures enable GBM in vivo‐like morphologies, and the results show a higher DNA double‐strand breakage in GBM monoculture samples when compared to the U251/HUVECs co‐culture, with cells in 2D featuring a larger number of DNA damage foci when compared to cells in 3D. The discrepancy in terms of proton radiation response indicates a difference in the radioresistance of the GBM cells mediated by the presence of HUVECs and the possible induction of stemness features that contribute to radioresistance and improved DNA repair.

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New Cellular Dimensions on Glioblastoma Progression

Cited by 8 publications

References 22 publications

Glioblastoma Therapy: Past, Present and Future

Glioblastoma Therapy: Past, Present and Future

The Drosophila Epidermal growth factor regulates Hedgehog-signalling cytoneme dynamics.

Micro‐Vessels‐Like 3D Scaffolds for Studying the Proton Radiobiology of Glioblastoma‐Endothelial Cells Co‐Culture Models

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