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Molecular Insights into Glioblastoma Pathogenesis: Focus on Progenitor Cells, Microglia and Noncoding RNA

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 20 March 2025 | Viewed by 2606

Special Issue Editor

Department of Biochemistry and Molecular Biology, Durham Research Center I, College of Medicine, University of Nebraska Medical Center, Room 7056, Omaha, NE, USA
Interests: oncology; anticancer; glioma; colon cancer; pancreatic cancer; chemoprevention; liquid biopsy; targeting; inhibitor

Special Issue Information

Dear Colleagues,

Glioblastoma (GBM) tumors are highly heterogeneous and encompass a wide range of cell types within a singular tumor. The tumor microenvironment (TME) niche comprises various components, including endothelial cells, neurons, astrocytes, oligodendrocytes, resident immune cells such as microglia, tumor-infiltrating circulating immune cells like TAMs, and noncellular elements such as apocrine and paracrine signaling molecules, exosomes, extracellular matrix (ECM) components, and secreted ECM remodeling enzymes. The diverse and dynamic character of the TME facilitates cancer cells' survival and treatment response. The communication between tumor cells and their surrounding cells is facilitated by soluble substances such as cytokines, chemokines, matrix remodeling enzymes, and growth factors. Moreover, it has been discovered that tumor cells employ many mechanisms, including exosomes, gap junctions, circulating tumor cells, tunneling nanotubes, cell-free DNA, and horizontal DNA transfer, to interact with both tumor and normal cells. The origins of GBM tumors continue to be a subject of continuing scholarly inquiry, wherein many cell types, including glia and neural stem cells (NSCs), are being investigated as potential contributors. Nevertheless, recent progress in RNA sequencing has provided further insights into the previously recognized variations within cancers. The observed enhancements have provided evidence that GBM tumor cells have transcriptional patterns that bear resemblance to neural progenitor cells (NPCs), oligodendrocyte precursor cells (OPCs), astrocytes (ACs), and mesenchymal (MES) cells at the cellular level. Therefore, in light of the current imperative to acquire additional understanding about the genesis and progression of GBM, as well as the reciprocal communication between tumor cells and the TME, in this Special Issue, we extend an invitation for the submission of reviews and research articles focusing on the early seeding phase of GBM tumorigenesis and the role of the heterogenous TME in its progression and invasion. 

Dr. Imran Khan
Guest Editor

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Keywords

  • glioblastoma
  • tumor microenvironment
  • microglia
  • tumor-infiltrating lymphocytes
  • astrocytes
  • progenitor cells
  • driver mutations

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Published Papers (2 papers)

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Research

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18 pages, 3243 KiB  
Article
Integrated Transcriptome Profiling and Pan-Cancer Analyses Reveal Oncogenic Networks and Tumor-Immune Modulatory Roles for FABP7 in Brain Cancers
by Yool Lee, Carlos C. Flores, Micah Lefton, Sukanya Bhoumik, Yuji Owada and Jason R. Gerstner
Int. J. Mol. Sci. 2024, 25(22), 12231; https://doi.org/10.3390/ijms252212231 - 14 Nov 2024
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Abstract
Fatty acid binding protein 7 (FABP7) is a multifunctional chaperone involved in lipid metabolism and signaling. It is primarily expressed in astrocytes and neural stem cells (NSCs), as well as their derived malignant glioma cells within the central nervous system. Despite growing evidence [...] Read more.
Fatty acid binding protein 7 (FABP7) is a multifunctional chaperone involved in lipid metabolism and signaling. It is primarily expressed in astrocytes and neural stem cells (NSCs), as well as their derived malignant glioma cells within the central nervous system. Despite growing evidence for FABP7’s tumor-intrinsic onco-metabolic functions, its mechanistic role in regulating the brain tumor immune microenvironment (TIME) and its impact on prognosis at the molecular level remain incompletely understood. Utilizing combined transcriptome profiling and pan-cancer analysis approaches, we report that FABP7 mediates the expression of multiple onco-immune drivers, collectively impacting tumor immunity and clinical outcomes across brain cancer subtypes. An analysis of a single-cell expression atlas revealed that FABP7 is predominantly expressed in the glial lineage and malignant cell populations in gliomas, with nuclear localization in their parental NSCs. Pathway and gene enrichment analysis of RNA sequencing data from wild-type (WT) and Fabp7-knockout (KO) mouse brains, alongside control (CTL) and FABP7-overexpressing (FABP7 OV) human astrocytes, revealed a more pronounced effect of FABP7 levels on multiple cancer-associated pathways. Notably, genes linked to brain cancer progression and tumor immunity (ENO1, MUC1, COL5A1, and IL11) were significantly downregulated (>2-fold) in KO brain tissue but were upregulated in FABP7 OV astrocytes. Furthermore, an analysis of data from The Cancer Genome Atlas (TCGA) showed robust correlations between the expression of these factors, as well as FABP7, and established glioma oncogenes (EGFR, BRAF, NF1, PDGFRA, IDH1), with stronger associations seen in low-grade glioma (LGG) than in glioblastoma (GBM). TIME profiling also revealed that the expression of FABP7 and the genes that it modulates was significantly associated with prognosis and survival, particularly in LGG patients, by influencing the infiltration of immunosuppressive cell populations within tumors. Overall, our findings suggest that FABP7 acts as an intracellular regulator of pro-tumor immunomodulatory genes, exerting a synergistic effect on the TIME and clinical outcomes in brain cancer subtypes. Full article
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Review

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37 pages, 2769 KiB  
Review
Status Quo in the Liposome-Based Therapeutic Strategies Against Glioblastoma: “Targeting the Tumor and Tumor Microenvironment”
by Mohd Haseeb, Imran Khan, Zeynep Kartal, Sadaf Mahfooz and Mustafa Aziz Hatiboglu
Int. J. Mol. Sci. 2024, 25(20), 11271; https://doi.org/10.3390/ijms252011271 - 19 Oct 2024
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Abstract
Glioblastoma is the most aggressive and fatal brain cancer, characterized by a high growth rate, invasiveness, and treatment resistance. The presence of the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB) poses a challenging task for chemotherapeutics, resulting in low efficacy, bioavailability, and [...] Read more.
Glioblastoma is the most aggressive and fatal brain cancer, characterized by a high growth rate, invasiveness, and treatment resistance. The presence of the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB) poses a challenging task for chemotherapeutics, resulting in low efficacy, bioavailability, and increased dose-associated side effects. Despite the rigorous treatment strategies, including surgical resection, radiotherapy, and adjuvant chemotherapy with temozolomide, overall survival remains poor. The failure of current chemotherapeutics and other treatment regimens in glioblastoma necessitates the development of new drug delivery methodologies to precisely and efficiently target glioblastoma. Nanoparticle-based drug delivery systems offer a better therapeutic option in glioblastoma, considering their small size, ease of diffusion, and ability to cross the BBB. Liposomes are a specific category of nanoparticles made up of fatty acids. Furthermore, liposomes can be surface-modified to target a particular receptor and are nontoxic. This review discusses various methods of liposome modification for active/directed targeting and various liposome-based therapeutic approaches in the delivery of current chemotherapeutic drugs and nucleic acids in targeting the glioblastoma and tumor microenvironment. Full article
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