Dataset Information

Candidate early biomarkers of Glioblastoma Multiforme revealed by longitudinal bottom-up proteomics study on multiple biofluids in a murine model

ABSTRACT: Glioblastoma Multiforme (GBM) is an aggressive form of brain tumor, associated with poor prognosis and low survival rates, and early diagnosis is impaired by the lack of presymptomatic biomarkers. Here we used a syngenic GBM mouse model to investigate longitudinal changes in the proteome profile of serum, serum small extracellular vesicles (sEVs) and cerebrospinal fluid (CSF) during GBM progression. Motor tests were used to define a baseline, a presymptomatic and an advanced stage of tumor progression and body fluids were sampled at these time points.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cerebrospinal Fluid, Blood Serum

DISEASE(S): Brain Glioblastoma Multiforme

SUBMITTER: Francesco Greco

LAB HEAD: Liam Andrew McDonnell

PROVIDER: PXD020285 | Pride | 2022-02-15

REPOSITORIES: Pride

ACCESS DATA

Publications

Longitudinal Bottom-Up Proteomics of Serum, Serum Extracellular Vesicles, and Cerebrospinal Fluid Reveals Candidate Biomarkers for Early Detection of Glioblastoma in a Murine Model.

Greco Francesco F Anastasi Federica F Pardini Luca Fidia LF Dilillo Marialaura M Vannini Eleonora E Baroncelli Laura L Caleo Matteo M McDonnell Liam A LA

Molecules (Basel, Switzerland) 20211002 19

Glioblastoma Multiforme (GBM) is a brain tumor with a poor prognosis and low survival rates. GBM is diagnosed at an advanced stage, so little information is available on the early stage of the disease and few improvements have been made for earlier diagnosis. Longitudinal murine models are a promising platform for biomarker discovery as they allow access to the early stages of the disease. Nevertheless, their use in proteomics has been limited owing to the low sample amount that can be collected ...[more]

PMID: 34641541

Similar Datasets

Project description:This study presents statistical analyses of gene expression in 5, 10 and 15 day post-fertilization (dpf) embryos of the teleost Fundulus heteroclitus treated with control vehicle (DMSO) or a potent non-ortho-PCB (PCB-126; 3,3’,4,4’,5-pentachlorobiphenyl). The embryos were from two populations: a clean, reference population (SC, Scorton Creek, MA USA) and a polluted Superfund population (N, New Bedford Harbor, MA USA). For each site, eggs from 8 females (~1100 total) were fertilized using minced testes from 5 males. After non-fertile eggs were culled, embryos were exposed to vehicle (DMSO; 0.1%) or PCB-126 (50 nM) in filtered seawater (salinity 25 part per thousand, 65 embros per 20 ml in glass petri dish) for 4 hr at 20º C. After exposure, the embryos were washed in filtered seawater and incubated at 20º C under a 14-h light, 10-h dark cycle. At 5-, 10-, and 15-dpf, embryos were collected as three pools of 20 embryos from each treatment group and flash frozen in liquid nitrogen and stored at -80º C until used for RNA isolation. A loop design was used for the microarray hybridizations where each sample is hybridized to 2 arrays using both Cy3 and Cy5 labeled fluorophores. We used three loops in which each loop consisted of Cy3- and Cy5-labeled embryo aRNAs from 12 samples: one sample from each population-treatment-time combination. Within a population-treatment-time, embryos were randomly assigned to one of the three loops. In total, 36 embryos were hybridized to 36 microarrays. The loops formed were SC5C→ SC5P → NBH5C→ NBH5P →SC10C→ SC10P→ NBH10C→ NBH10P → SC15C→ SC15P → NBH15C → NBH15P → SC5C, where each arrow represents a separate hybridization (array) with the biological sample at the base of the arrow labeled with Cy3 and the biological sample at the head of the arrow labeled with Cy5. SC represents the Scorton Creek, Sandwich, MA population (reference), NBH represents the New Bedford Harbor, MA population, C represents control dose (DMSO), P represents the PCB-126 dose, 5 represents 5 dpf, 10 represents 10 dpf and 15 represents 15 dpf.

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

Candidate early biomarkers of Glioblastoma Multiforme revealed by longitudinal bottom-up proteomics study on multiple biofluids in a murine model

Publications

Longitudinal Bottom-Up Proteomics of Serum, Serum Extracellular Vesicles, and Cerebrospinal Fluid Reveals Candidate Biomarkers for Early Detection of Glioblastoma in a Murine Model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure