CSIG-09. PROTEOMIC ANALYSIS OF MENINGIOMA CELL-DERIVED EXTRACELLULAR VESICLES: FIRST OF A KIND. (11th November 2019)

• Record Type: Journal Article
• Authors: Ricklefs, Franz; Fuh, Manka; Maire, Cecile; Holz, Mareike; Kolbe, Katharina; Westphal, Manfred; Schlüter, Hartmut; Lamszus, Katrin
• Is Part Of: Neuro-oncology. Volume 21(2019)Supplement 6
• Page Start: vi45
• Page End: vi46
• Publication Date: 2019-11-11
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noz175.180
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: BACKGROUND: Extracellular vesicles (EVs) play an important role in cell-cell communication in different types of tumors, carrying multiple layers of biological functional molecules, including proteins, RNA, DNA and lipids. Their implication as biomarkers in tumor disease is under current investigation. We previously showed that EVs in glioblastoma reflect the tumor subtype and that glioblastoma patients have elevated circulating particle counts. Regarding to meningioma, it is not known to what extent these usually benign tumors secrete EVs and how these EVs reflect the tumor. Here we report the first study that analyzed meningioma cell-derived EVs. METHODS: Meningioma tissue, short-term cell cultures and cell culture-derived EVs (menEVs), (n=4) were analyzed by global mass-spectromety, immunoblotting and imaging flow cytometry and compared to EVs from glioblastoma short-term cell cultures (gEVs), (n=4). Plasma EVs from meningioma patients (n = 12) were analyzed for their tetraspanin marker expression (CD9, CD81 and CD63). EVs were further analyzed by nanoparticle analysis (NTA) and electron microscopy. RESULTS: menEVs were 110-140nm in size and exhibited vesicular structures by electron microscopy. We identified 269 proteins in menEVs through mass spectometry. 45 proteins were upregulated in menEVs compared to short-term cell culture and original tumor tissue. 99 proteins were exclusively found in menEVs compared to gEVs, with osteopontin being the top highly expressed protein within the mEV fraction. Both meningioma and glioblastoma patients have elevated circulating plasma EV counts (p< 0.01), as measured by NTA. CONCLUSION: The increase in circulating plasma EVs in meningioma patients suggests that tumor cell-derived EVs augment the pool of circulating EVs and could be utilized to obtain information on the tumor by liquid biopsy. Osteopontin is known to be expressed at high levels in meningiomas and its association with menEVs may facilitate isolation of circulating meningioma-specific EVs for analysis.