Dataset Information

Functional genomics of glioblastoma: from epigenetics to proteomic investigation of tumor-initiating cell secretome

ABSTRACT: The main objectives of the project are as follows: 1) Deciphering the TIC specific secretome signature. The secretome collected from four different TICs and their corresponding differentiated cell cultures will be subjected to label-free quantitative proteomic analysis to identify a TIC specific secretome signature. 2) Validation and functional characterization of selected molecules from TIC specific secretome signature. Selected molecules based on the level of regulation and literature information will be validated at the level of transcript and protein. The importance of a set of validated proteins will be studied both in vitro using neurosphere cultures and angiogenesis assays, and in vivo using an intracranial glioma model in nude mice 3) Characterizing of GBM specific serum proteome signature. Using label-free quantitative proteomics, we will compare the serum proteome of tumor bearing mice (xenotransplantated with TICs), early after tumor establisment and after the tumor has reached its maximum size.We will also explore by targeted quantitative proteomics whether the level of “specific” TIC-secreted proteins is increased in the serum of TIC initiated GBM bearing mice and verify, using the same strategy, proteins found to be differentially expressed in serum in both mice groups. These studies will reveal whether TIC-secreted proteins (and/or other GBM-derived proteins) can be retrieved in serum and thus be considered as candidate biomarkers of GBM.

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Glioblastoma

SUBMITTER: Functional Proteomics Platform FPP

LAB HEAD: Prof. Kumaravel Somasundaram

PROVIDER: PXD032958 | Pride | 2022-06-07

REPOSITORIES: Pride

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Publications

Differentiated glioma cell-derived fibromodulin activates integrin-dependent Notch signaling in endothelial cells to promote tumor angiogenesis and growth.

Sengupta Shreoshi S Mondal Mainak M Prasasvi Kaval Reddy KR Mukherjee Arani A Magod Prerna P Urbach Serge S Friedmann-Morvinski Dinorah D Marin Philippe P Somasundaram Kumaravel K

eLife 20220601

Cancer stem cells (CSCs) alone can initiate and maintain tumors, but the function of non-cancer stem cells (non-CSCs) that form the tumor bulk remains poorly understood. Proteomic analysis showed a higher abundance of the extracellular matrix small leucine-rich proteoglycan fibromodulin (FMOD) in the conditioned medium of differentiated glioma cells (DGCs), the equivalent of glioma non-CSCs, compared to that of glioma stem-like cells (GSCs). DGCs silenced for FMOD fail to cooperate with co-impla ...[more]

PMID: 35642785

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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

Functional genomics of glioblastoma: from epigenetics to proteomic investigation of tumor-initiating cell secretome

Publications

Differentiated glioma cell-derived fibromodulin activates integrin-dependent Notch signaling in endothelial cells to promote tumor angiogenesis and growth.

Similar Datasets

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