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Biology subjects

Stylli, S.

Publications and source records attributed to Stylli, S..

2 recordsLinked to original sources

Proteome of human glioblastoma and meningioma tissue small extracellular vesicles

Small extracellular vesicles have gained attention in neuroscience due to their role in cell-to- cell communication and their potential diagnostic and therapeutic applications. Despite progress in the field, there remains a gap in our understanding of the composition and function of extracellular vesicles with regards to brain tumours. Previous studies have primarily evaluated extracellular vesicles obtained from patient fluids or cell culture medium, rather than directly from tumour tissue. Here we successfully isolated small extracellular vesicles from surgical tissue biopsies of glioblastomas or meningiomas, marking, marking the first report of in situ extracellular vesicle isolation from brain tumours. The protein content of the tumour tissue and their extracellular vesicles was characterized using tandem mass spectrometric proteomics, revealing proteins exclusively detected or enriched in extracellular vesicles relative to the tumour tissue. While our study confirmed proteins previously identified in glioblastoma and meningioma extracellular vesicles from various sources, it also identified novel proteins and pathways associated with extracellular vesicles from these tumour types. This study underscores the benefit of analysing in situ extracellular vesicles derived directly from brain tissue for insights into tumour biology and highlights the need for further research comparing extracellular vesicles from various types and grades of brain tumours.

biochemistry↗

Intratumoral MAPK and PI3K signaling pathway heterogeneity in glioblastoma tissuecorrelates with selective CREB signaling and specific functional gene signatures

Limitations in discovering useful tumor biomarkers and drug targets is not only due to patient-to-patient differences but also due to intratumoral heterogeneity. Heterogeneity arises due to the genetic and epigenetic variation of tumor cells in response to microenvironmental interactions and cytotoxic therapy. We explored specific signaling pathway activation in glioblastoma (GBM) by investigating the intratumoral activation of the MAPK and PI3K pathways. We present data demonstrating a striking preponderance for mutual exclusivity of MAPK and PI3K activation in GBM tissue, where MAPK activation correlates with proliferation and transcription factor CREB activation and PI3K activation correlates with CD44 expression. Bioinformatic analysis of signaling and CREB-regulated target genes supports the immunohistochemical data, showing that the MAPK-CREB activation correlates with proliferative regions. In-silico analysis suggests that MAPK-CREB signaling activates a pro-inflammatory molecular signature and correlates with a mesenchymal GBM subtype profile, while PI3K-CREB activation correlates with the proneural GBM subtype and a tumor cell invasive gene signature. Overall, the data suggests the existence of intratumoral subtype heterogeneity in GBM and that using combinations of both MAPK and PI3K drug inhibitors is necessary for effective targeted therapy.

pathology↗