Dataset Information

Metabolic Reprogramming into a Glycolysis Phenotype Induced by Extracellular Vesicles derived from Prostate Cancer Cells

ABSTRACT: . Quantitative proteomics between EVs derived from PC-3 and PC-3AcT cells identified the 935 confident EV proteins. According to the cellular adaptation to lactic acidosis, we revealed 159 regulated EV proteins related in energy metabolism, cellular shape, and extracellular matrix. Further, these EVs contains the high abundance of glycolytic enzymes and in particular PC-3AcT EVs were enriched with apolipoproteins including apolipoprotein B100 (APOB)

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell, Cell Culture

DISEASE(S): Prostate Adenocarcinoma

SUBMITTER: Dongsic Choi

LAB HEAD: Dongsic Choi

PROVIDER: PXD054467 | Pride | 2025-04-10

REPOSITORIES: Pride

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			Action	DRS
	20220812_SCHuni_4_PC3_1.mzXML	Mzxml
	20220812_SCHuni_4_PC3_1.raw	Raw
	20220812_SCHuni_5_PC3_2.mzXML	Mzxml
	20220812_SCHuni_5_PC3_2.raw	Raw
	20220812_SCHuni_6_PC3_3.mzXML	Mzxml

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Project description:Most cancer cells adopt a less efficient metabolic process of aerobic glycolysis with high level of glucose uptake followed by lactic acid production, known as the Warburg effect. This phenotypic transition enables cancer cells to achieve increased cellular survival and proliferation in a harsh low-oxygen tumor microenvironment. Also, the resulting acidic microenvironment causes inactivation of the immune system such as T-cell impairment that favours escape by immune surveillance. While lots of studies have revealed that tumor-derived EVs can deliver parental materials to adjacent cells and contribute to oncogenic reprogramming, their functionality in energy metabolism is not well addressed. In this study, we established prostate cancer cells PC3-AcT resistant to cellular death in an acidic culture medium driven by lactic acid. Quantitative proteomics between EVs derived from PC-3 and PC-3AcT cells identified 935 confident EV proteins. According to cellular adaptation to lactic acidosis, we revealed 159 regulated EV proteins related to energy metabolism, cellular shape, and extracellular matrix. These EVs contained a high abundance of glycolytic enzymes. In particular, PC-3AcT EVs were enriched with apolipoproteins including apolipoprotein B100 (APOB). APOB on PC-3AcT EVs could facilitate their endocytic uptake depending on low density lipoprotein receptor of recipient PC-3 cells, encouraging increases of cellular proliferation and survival in acidic culture media via increased activity and expression of hexokinases and phosphofructokinase. The activation of recipient PC-3 cells can increase glucose consumption and ATP generation, representing an acquired metabolic reprogramming into the Warburg phenotype. Our study first revealed that EVs derived from prostate cancer cells could contribute to energy metabolic reprogramming and that the acquired metabolic phenotypic transition of recipient cells could favor cellular survival in tumor microenvironment.

Project description:Glioblastoma multiforme (GBM) is a highly aggressive and heterogeneous form of primary brain tumors, driven by a complex repertoire of oncogenic alterations, including the constitutively active epidermal growth factor receptor (EGFRvIII). EGFRvIII impacts both cell-intrinsic and non-cell autonomous aspects of GBM progression, including cell invasion, angiogenesis and modulation of the tumor microenvoiront, this is, at least in part, attributable to the release and intercellular trafficking of extracellular vesicles (EVs), heterogeneous membrane structures containing multiple bioactive macromolecules. Here we analyzed the impact of EGFRvIII on the profile of glioma EVs using a series of isogenic tumor cell lines, in which this oncogene exhibits a strong transforming activity. Thus, we observed that EGFRvIII expression alters several properties of glioma EVs, including their output and global protein composition. Using mass spectrometry, quantitative proteomic analysis and Gene Ontology terms filters, we observed that EVs released by EGFRVIII-transformed cells were enriched for extracellular exosome and focal adhesion related proteins. Among them, we validated the association of pro-invasive proteins (CD44, BSG, CD151) with EVs of EGFRvIII expressing cells, and down-regulation of exosomal markers (CD81 and CD82) in EVs of their indolent counterparts. Nano-flow cytometry revealed that the EV output from individual glioma cell lines was highly heterogeneous, such that only a fraction of EVs contained specific proteins such as EGFR, CD9, or others. Notably, cells expressing EGFRvIII released ample EVs double positive for CD44/BSG, and these proteins also co-localized in cellular filopodia. We also detected the expression of homophilic adhesion molecules and increased homologous EV uptake by EGFRvIII-positive glioma cells. These results suggest that oncogenic EGFRvIII reprograms the proteome of GBM-related EVs, a notion with considerable implications for their biological activity and properties relevant for development of EV-based cancer biomarkers.

Dataset Information

Metabolic Reprogramming into a Glycolysis Phenotype Induced by Extracellular Vesicles derived from Prostate Cancer Cells

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