Dataset Information

Glioma-derived IL-33 orchestrates an inflammatory brain tumor microenvironment that accelerates glioma progression

ABSTRACT: In order to further understand how glioma-derived IL-33 is orchestrating changes within the tumor microenvironment and based on the significant increase of anti-inflammatory mediators including a number of signaling molecules observed in IL-33+ tumors, we performed phospho-proteomic analysis using mass spectrometry on the brains of tumor-bearing mice.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

TISSUE(S): Brain

DISEASE(S): Brain Glioblastoma Multiforme

SUBMITTER: Shyam Menon

LAB HEAD: Stephen Mark Robbins

PROVIDER: PXD021100 | Pride | 2020-08-28

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	Natalie-1.mzid_Natalie-1.MGF	Mzid
	Natalie-10.mzid_Natalie-10.MGF	Mzid
	Natalie-1peptides_1_0_0.mzid.mzid_Natalie-1_peptides_1_0_0.mzid.MGF	Mzid
	Natalie-4.mzid_Natalie-4.MGF	Mzid
	Natalie-4peptides_1_0_0.mzid.mzid_Natalie-4_peptides_1_0_0.mzid.MGF	Mzid

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Publications

Glioma-derived IL-33 orchestrates an inflammatory brain tumor microenvironment that accelerates glioma progression.

De Boeck Astrid A Ahn Bo Young BY D'Mello Charlotte C Lun Xueqing X Menon Shyam V SV Alshehri Mana M MM Szulzewsky Frank F Shen Yaoqing Y Khan Lubaba L Dang Ngoc Ha NH Reichardt Elliott E Goring Kimberly-Ann KA King Jennifer J Grisdale Cameron J CJ Grinshtein Natalie N Hambardzumyan Dolores D Reilly Karlyne M KM Blough Michael D MD Cairncross J Gregory JG Yong V Wee VW Marra Marco A MA Jones Steven J M SJM Kaplan David R DR McCoy Kathy D KD Holland Eric C EC Bose Pinaki P Chan Jennifer A JA Robbins Stephen M SM Senger Donna L DL

Nature communications 20201005 1

Despite a deeper molecular understanding, human glioblastoma remains one of the most treatment refractory and fatal cancers. It is known that the presence of macrophages and microglia impact glioblastoma tumorigenesis and prevent durable response. Herein we identify the dual function cytokine IL-33 as an orchestrator of the glioblastoma microenvironment that contributes to tumorigenesis. We find that IL-33 expression in a large subset of human glioma specimens and murine models correlates with i ...[more]

PMID: 33020472

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Project description:IL-33 is a nuclear cytokine from the IL-1 family that plays important roles in health and disease. Under healthy conditions, IL-33 is constitutively expressed to high levels in the nucleus of producing cells in various human and mouse tissues. The extracellular function of IL-33 cytokine has been well documented, but it remains unclear whether intracellular nuclear IL-33 has additional functions in the nucleus. Here, we used a global proteomic approach based on quantification of 5000 individual proteins by high-resolution mass spectrometry to compare the extracellular and intracellular roles of IL-33 in primary human endothelial cells, a major source of IL-33 protein in human tissues. Large-scale analysis of protein expression was performed either after stimulation of the cells with the IL-33 mature form IL-3395-270 (during 6h or 24h) or after siRNA knockdown of intracellular IL-33 (two experiments, each with a different pool of distinct siRNAs, noted siRNA1 and siRNA2). In each case, proteins were fractionated by 1D SDS-PAGE in 12 gel bands, and label-free quantitative analysis was performed. The present dataset contains the files for the two experiments of knockdown of endogenous nuclear IL-33 expression: - RNA silencing strategy 1. Knockdown of endogenous nuclear IL-33 expression was performed with a pool of four distinct siRNAs (Dharmacon ON-TARGETplus SMARTpool IL-33 siRNAs) that have been specifically modified for efficient silencing of the target gene with reduced off-target effects. Cells transfected with these siRNA duplexes (si1) were compared with those transfected with the provided controls (CTsi1). Three independent biological replicates (noted _A, _B, _C) were prepared and analyzed for each condition, leading to 6 different samples. Each of them was fractionated into 12 gel bands analyzed by nanoLC-MS/MS, leading to 72 raw files. - RNA silencing strategy 2. The second knockdown strategy was based on the use of an independent pool of three siRNAs targeting IL-33, predesigned by another provider using new and critical siRNA design rules (Sigma MISSION Predesigned Il-33 siRNAs based on Rosetta siRNA design algorithm). Cells transfected with these siRNA duplexes (si2) were compared with those transfected with the provided controls (CTsi2). Three independent biological replicates (noted _A, _B, _C) were prepared and analyzed for each condition, leading to 6 different samples. Each of them was fractionated into 12 gel bands analyzed by nanoLC-MS/MS, leading to 72 raw files.