Dataset Information

Glioblastoma progression is hindered by melatonin-primed mesenchymal stromal cells through dynamic intracellular and extracellular reorganizations

ABSTRACT: Background. Glioblastoma (GBM) is the deadliest form of brain cancer and its treatment remains an unresolved challenge. Mesenchymal stromal cells (MSCs) have been explored as vehicles for the targeted delivery of anticancer drugs due to their tumor-homing abilities. However, their clinical application is limited due to the controversial role of MSCs on carcinogenesis. This study investigates how MSCs influence tumor behavior and explores the synergistic anticancer effects of the cytoprotective melatonin (Mel). Methods. Orthotopic and subcutaneous GBM xenograft mouse models were used to assess the antitumor effect of Mel pre-treated MSCs (MSCMel). Histological, immunohistochemistry and ultrastructural analysis were conducted to identify phenotypic changes in the tumors. A set of in vitro assays, including direct and indirect co-cultures, dynamic single-cell tracking and tumorsphere migration assay, was conducted to explore the impact of MSCMel on primary and non-primary GBM cells. Transcriptome profiling was used to identify genes and pathways modulated by the synergistic therapy. Results. MSCMel delayed tumor growth in mice and increased collagen deposition. Additionally, MSCMel showed enhanced capacity to prevent GBM cell migration than untreated MSCs. Molecular analysis identified genes and pathways related to cell migration, cytoskeletal dynamics and extracellular matrix remodeling in GBM cells exposed to MSCMel, including extensive reduction of vimentin expression. Finally, a gene signature associated with the clinical outcomes of GBM patients was identified. Conclusions. Our study demonstrates that melatonin enhances the anticancer properties of MSCs, providing new insights on their interaction with GBM cells and the tumor environment. These findings offer valuable guidance for advancing MSC-based therapies in clinical practice.

ORGANISM(S): Homo sapiens

PROVIDER: GSE268582 | GEO | 2025/03/19

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Glioblastoma (GBM), the most malignant primary brain tumor, is characterized by widespread heterogeneity, leading to poor and unpredictable clinical outcomes. Recent studies have provided evidences that the tumor microenvironment has a critical role in regulating tumor growth by establishing a complex network of interactions with tumor cells. Here we investigate how GBM cells modulate glial cells, and how this modulation can influence back on the malignant phenotype of GBM cells. Primary mouse glial cultures were established and cultured in serum-free media (unprimed) or exposed to secretome derived from GL261 GBM cells (primed). Conditioned media (CM) from each glial culture were collected and a proteomic analysis was conducted. Glial cells CM (unprimed and primed) were also used in GL261 GBM cells to evaluate its impact in critical hallmarks of GBM cells, including viability, migration, and activation of tumor-related intracellular signaling pathways. The proteomic analysis revealed that the pre-exposure of glial cells to CM from GBM cells led to the upregulation of several proteins related to inflammatory response, cell adhesion and extracellular structure organization within the secretome of primed glial cells, consistent with a pattern of reactive astrogliosis. At the functional levels, CM derived from unprimed glial cells favored an increase in cell migration capacity, while CM from primed glial cells was more efficient in promoting GBM cells viability. These effects on GBM cells were accompanied by activation of particular intracellular cancer-related pathways, mainly the MAPK/ERK pathway, which is a known regulator of cell proliferation. Together, our results demonstrate that glial cells can have a different impact on the progression of GBM tumors, suggesting that the secretome of GBM cells is able to modulate the secretome of neighboring glial cells, in a way that regulates the “go-or-grow” phenotypic switch of GBM cells. Together, our results suggest that glial cells can impact on the pathophysiology of GBM tumors, and that the secretome of GBM cells is able to modulate the secretome of neighboring glial cells, in a way that regulates the “go-or-grow” phenotypic switch of GBM cells.

Dataset Information

Glioblastoma progression is hindered by melatonin-primed mesenchymal stromal cells through dynamic intracellular and extracellular reorganizations

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets