Abstract
Although histologically benign, adamantinomatous craniopharyngioma (AC) pediatric brain tumor is a locally aggressive disease that frequently determines symptoms and hormonal dysfunctions related to the mass effect on the surrounding structures. Another typical feature of this benign neoplasm is the presence of voluminous liquid cysts frequently associated with the solid component. Even if studies have been devoted to the proteomic characterization of the tumor intracystic fluid, poor explorations have been performed on its solid part, principally investigated by transcriptomics technologies. In the present study, seven specimens of AC whole tumor tissue have been analyzed by LC-MS for a preliminary assessment of the proteomic profile by a top-down/bottom-up integrated approach. Thymosin beta 4, ubiquitin, calmodulin, S100 proteins, prothymosin α isoform 2, alpha-defensins 1-4, and fragments largely belonging to vimentin, hemoglobin, and glial fibrillary acidic protein characterized the intact proteome. The identification of alpha-defensins, formerly characterized in AC intracystic fluid, reinforces the hypothesis of a role for inflammation in tumor pathogenesis. A total number of 1798 unique elements were identified by a bottom-up approach with a special focus on the 433 proteins commonly characterized in the 85.7% of the samples analyzed. Their gene ontology classification evidenced the involvement of the adherence system, intermediate filaments, and actin cytoskeleton in tumor pathogenesis and of elements part of the Wnt, FGF, and EGFR signaling pathways. In addition, proteins involved in calcium modulation, innate immunity, inflammation, CCKR and integrin signaling, and gonadotropin-releasing hormone receptor pathways were also outlined. Further than confirming proteomic data previously obtained on AC intracystic fluid, these results offer a preliminary overview of the AC whole tissue protein phenotype, adding new hints towards the comprehension of this still obscure pediatric brain tumor.
Highlights
Adamantinomatous craniopharyngioma (AC) is the most common sellar tumor in the pediatric age representing5-11% of intracranial tumors with an incidence of 1.532.92/100000 per year under 15 years [1, 2]
LC-MS top-down and bottom-up proteomic analysis was performed on whole AC tissues to characterize the proteome in either its entire or its digested form and to disclose common proteomic signatures
The LC-MS data obtained by the analysis of the undigested protein extracts of AC tissue homogenates have been elaborated by both Proteome Discoverer 1.4 software and manual inspection of the MS and MS/MS spectra recorded along the chromatogram
Summary
Adamantinomatous craniopharyngioma (AC) is the most common sellar tumor in the pediatric age representing5-11% of intracranial tumors with an incidence of 1.532.92/100000 per year under 15 years [1, 2]. Cluster cells were investigated for their paracrine signaling activity by RNA profiling, showing overexpression, with respect to the palisading epithelium and reactive glia, of multiple ligands and secreted factors of FGF, BMP, Wnt, SHH, MAPK/ERK, and TGFβ pathways, responsible for the activation of this signaling in the neighboring cells. On this basis, preclinical studies in vitro on human and mouse AC of the MAPK/ERK pathway inhibitor drug trametinib resulted to be promising for potential AC treatment [15]. ELISA analysis of cytokines showed activation of the inflammasome complex in AC, with the probable involvement of cholesterol
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
