On the origin and development of glioblastoma: multifaceted role of perivascular mesenchymal stromal cells

Ah-Pine, Franck; Khettab, Mohamed; Bedoui, Yosra; Slama, Yosr; Daniel, Matthieu; Doray, Bérénice; Gasque, Philippe

doi:10.1186/s40478-023-01605-x

Cited by 18 publications

(8 citation statements)

References 159 publications

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“…These studies have recently been reviewed comprehensively by Betsholtz et al in 2022 [66]. All these studies support the emerging notion that periendothelial cells such as PCs (in close association with the basement membrane of endothelial cells) can give rise to pMSCs detaching from the vessels and infiltrating the tissue parenchyma [63,67]. Inversely, in zebrafish, pMSCs have been shown to give rise to PCs to support vessel survival/growth [68].…”

Section: Origin Of Mesenchymal Stem Cells and Other Stromal Cells In ...mentioning

confidence: 76%

The Dual Role of Mesenchymal Stem Cells in Cancer Pathophysiology: Pro-Tumorigenic Effects versus Therapeutic Potential

Slama,

Ah-Pine,

Khettab

et al. 2023

IJMS

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Mesenchymal stem/stromal cells (MSCs) are multipotent cells involved in numerous physiological events, including organogenesis, the maintenance of tissue homeostasis, regeneration, or tissue repair. MSCs are increasingly recognized as playing a major, dual, and complex role in cancer pathophysiology through their ability to limit or promote tumor progression. Indeed, these cells are known to interact with the tumor microenvironment, modulate the behavior of tumor cells, influence their functions, and promote distant metastasis formation through the secretion of mediators, the regulation of cell–cell interactions, and the modulation of the immune response. This dynamic network can lead to the establishment of immunoprivileged tissue niches or the formation of new tumors through the proliferation/differentiation of MSCs into cancer-associated fibroblasts as well as cancer stem cells. However, MSCs exhibit also therapeutic effects including anti-tumor, anti-proliferative, anti-inflammatory, or anti-oxidative effects. The therapeutic interest in MSCs is currently growing, mainly due to their ability to selectively migrate and penetrate tumor sites, which would make them relevant as vectors for advanced therapies. Therefore, this review aims to provide an overview of the double-edged sword implications of MSCs in tumor processes. The therapeutic potential of MSCs will be reviewed in melanoma and lung cancers.

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Section: Origin Of Mesenchymal Stem Cells and Other Stromal Cells In ...mentioning

confidence: 76%

The Dual Role of Mesenchymal Stem Cells in Cancer Pathophysiology: Pro-Tumorigenic Effects versus Therapeutic Potential

Slama,

Ah-Pine,

Khettab

et al. 2023

IJMS

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“…GBM cell lines were seeded into 24-well plates with 500 μL of a prepared cell suspension containing 100,000 cells/mL per well, resulting in a total of 50,000 cells in each well. These plates were then incubated for 24 hours at 37°C with 5% CO 2 .…”

Section: Evaluation Of Intracellular Oxidative Stress After Mono and ...mentioning

confidence: 99%

“…2 that mainly arise from stem or progenitor cells and that confer great intra-and intertumoral heterogeneity [2].…”

Section: Introductionmentioning

confidence: 99%

Enhancing Therapeutic Approaches in Glioblastoma with Prooxidant Treatments and Synergistic Combinations: <em>In Vitro</em> Experience of Doxorubicin and Photodynamic Therapy

Cesca,

Caverzan,

Lamberti

et al. 2024

Preprint

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Glioblastoma (GBM) is an aggressive brain cancer characterized by significant molecular and cellular heterogeneity, complicating treatment efforts. Current standard therapies, including surgical resection, radiation, and temozolomide (TMZ) chemotherapy, often fail to achieve long-term remission due to tumor recurrence and resistance. A pro-oxidant environment is in-volved in glioma progression, with oxidative stress contributing to the genetic instability that leads to gliomagenesis. However, the generation of reactive oxygen species (ROS) results in the dysregulation of antioxidant defenses in GBM cells, creating a vulnerability that can be thera-peutically exploited. Evaluating pro-oxidant therapies in brain tumors is crucial due to their po-tential to selectively target and eradicate cancer cells by exploiting the elevated oxidative stress levels inherent in these malignant cells, thereby offering a novel and effective strategy for overcoming resistance to conventional therapies. This study investigates the therapeutic potential of doxorubicin (DOX) and photodynamic therapy (PDT) with Me-ALA, focusing on their effects on redox homeostasis. Basal ROS levels and antioxidant gene expression (NFE2L2, CAT, GSR) were quantitatively assessed across GBM cell lines, revealing significant variability probably linked to genetic differences. DOX and PDT treatments, both individually and in combination, were ana-lyzed for their efficacy in inducing oxidative stress and cytotoxicity. An in silico analysis further explored the relationship between gene mutations and oxidative stress in GBM patients, providing insights into the molecular mechanisms underlying treatment responses. Our findings suggest that pro-oxidant therapies, such as DOX and PDT in combination, could selectively target GBM cells, highlighting a promising avenue for improving therapeutic outcomes in GBM.

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“…Moreover, mesenchymal GSCs are enriched with genes associated with angiogenesis, inflammation, and cell migration/invasion. They tend to develop immunosuppression and exhibit increased radio/chemoresistance, all of which are features linked to a worse prognosis [ 36 , 37 , 38 , 39 ]. In any of the cases, the survival difference is minimal because both subtypes can coexist in the same tumor, and dynamic transitions from a proneural to a mesenchymal phenotype can be induced by TNF-α, temozolomide (TMZ), or radiation through an NF-κB-dependent mechanism [ 20 , 36 , 40 , 41 ].…”

Section: Introductionmentioning

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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On the origin and development of glioblastoma: multifaceted role of perivascular mesenchymal stromal cells

Cited by 18 publications

References 159 publications

The Dual Role of Mesenchymal Stem Cells in Cancer Pathophysiology: Pro-Tumorigenic Effects versus Therapeutic Potential

The Dual Role of Mesenchymal Stem Cells in Cancer Pathophysiology: Pro-Tumorigenic Effects versus Therapeutic Potential

Enhancing Therapeutic Approaches in Glioblastoma with Prooxidant Treatments and Synergistic Combinations: <em>In Vitro</em> Experience of Doxorubicin and Photodynamic Therapy

Glioblastoma Therapy: Past, Present and Future

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