Dataset Information

Mapping the invasive network of glioblastoma by proteomics from laser-capture microdissected samples

ABSTRACT: Glioblastomas are brain tumors that are derived from astrocytes or oligodendrocytes. These tumors have a heterogeneous structure composed of a necrotic and vascularized center and an invasive periphery. The rapid development of glioblastoma and its ability to invade surrounding tissues makes it a complex pathology to treat, and the average survival of patients ranging from 12 to 15 months. The first and second lines of treatment, based on the Stupp protocol, consisting of the resection of the tumor mass and adjuvant temozolomide treatment and/or radiotherapy, only allow delaying recurrence for a few months. The additional use of anti-angiogenic treatment, despite its initial effects on tumor vascularization and the central tumor core, invariably leads to tumor escape. Tumor cell invasion is the central element in tumor recurrence. It is therefore important to understand the mechanisms of tumor invasion and understand the interactions between tumor cells and their microenvironment. Here, we performed proteomics analysis of glioblastoma core and invasive areas, tumor derived from a patient xenograft. Bioinformatics data analysis allowed us to identify molecules that may represent markers of tumor invasion. We established novel protein signatures such as phopholipoprotein-1 (PLP1), 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNP) or Dynamin-1 (DNM1), and validated them in tumor samples. Finally, a functional validation was carried out in in vitro experiments. To conclude, our results report novel unexpected proteins that are involved in GBM invasion and that may constitute novel therapeutic targets.

INSTRUMENT(S): Q Exactive

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

TISSUE(S): Brain

DISEASE(S): Brain Glioblastoma Multiforme

SUBMITTER: Dupuy Jean-William

LAB HEAD: Thomas Daubon

PROVIDER: PXD012791 | Pride | 2021-06-10

REPOSITORIES: Pride

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Publications

The invasive proteome of glioblastoma revealed by laser-capture microdissection.

Daubon Thomas T Guyon Joris J Raymond Anne-Aurélie AA Dartigues Benjamin B Rudewicz Justine J Ezzoukhry Zakaria Z Dupuy Jean-William JW Herbert John M J JMJ Saltel Frédéric F Bjerkvig Rolf R Nikolski Macha M Bikfalvi Andreas A

Neuro-oncology advances 20190501 1

<h4>Background</h4>Glioblastomas are heterogeneous tumors composed of a necrotic and tumor core and an invasive periphery.<h4>Methods</h4>Here, we performed a proteomics analysis of laser-capture micro-dissected glioblastoma core and invasive areas of patient-derived xenografts.<h4>Results</h4>Bioinformatics analysis identified enriched proteins in central and invasive tumor areas. Novel markers of invasion were identified, the genes proteolipid protein 1 (PLP1) and Dynamin-1 (DNM1), which were ...[more]

PMID: 32642662

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Project description:Pituitary adenomas are common benign neoplasms giving rise to disorders of growth, reproductive function and cortisol production. Although recently determined to be monoclonal, very little is known about the mechanisms regulating the development of pituitary hyperplasia and neoplasia in humans. Surgical resection is the treatment of choice for most symptomatic pituitary adenomas. The goal of surgery is the complete removal of the tumor and the success of surgery is strongly affected by the presence of local invasion. However, complete tumor removal is unlikely when there is extensive local invasion. Identifying genes that control the invasiveness and recurrence of this class of tumors will provide therapeutic targets for this class of tumors. We will determine the expression pattern of genes in recurrent and invasive and pituitary adenomas and compare those to non-invasive and non-recurrent tumors. We hypothesize that the differential expression and activation of a number of genes affect pituitary adenoma recurrence and invasiveness. Rationale: Preliminary result showed a differential expression of novel PKC isozymes in non-invasive and invasive pituitary adenomas. PMA, an activator of both novel and classical PKC isozymes increased the expression of gelatinase A (MMP-2) mRNA in human pituitary adenoma cell line. This result raises a fundamental question as to the functional role of novel PKC isozymes and proteases in the invasive phenotype of pituitary adenomas. The primary component of this Specific Aim is to determine whether specific genes are differentially expressed in recurrent or invasive adenomas when compared with control non-invasive tumors. Tissue specimens from non-invasive and invasive (dural invasion based microscopic examination) and recurrent vs non-recurrent tumors will be used for microarray analysis. Frozen pituitaryspecimens will be collected and total RNA extracted with TriZol reagent. We will provide total RNA (10 ug) from non-invasive, invasive, reoccurred and non-occurrent pituitary adenomas.

Dataset Information

Mapping the invasive network of glioblastoma by proteomics from laser-capture microdissected samples

Publications

The invasive proteome of glioblastoma revealed by laser-capture microdissection.

Similar Datasets

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