The Ether Lipid Precursor Hexadecylglycerol Stimulates the Release and Changes the Composition of Exosomes Derived from PC-3 Cells

Phuyal, Santosh; Skotland, Tore; Hessvik, Nina Pettersen; Simolin, Helena; Øverbye, Anders; Brech, Andreas; Parton, Robert G.; Ekroos, Kim; Sandvig, Kirsten; Llorente, Alicia

doi:10.1074/jbc.m114.593962

Cited by 117 publications

(87 citation statements)

References 53 publications

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“…Interestingly, Phuyal et al recently reported that the ether lipid precursor hexadecylglycerol added to PC-3 cells doubled the cellular levels of ether lipids in the cells, with increased levels of ether lipids also observed in their exosomes. Furthermore, cells containing high levels of ether lipids were found to release more exosomes than control cells [57]. To date however, the possible functional role of ether lipids in exosome mediated intercellular signaling have not yet been explored.…”

Section: Resultsmentioning

confidence: 99%

Rapid and comprehensive ‘shotgun’ lipidome profiling of colorectal cancer cell derived exosomes

Lydic

Townsend

Adda

et al. 2015

Methods

167

184

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There is an increasing recognition of the role that cancer cell derived exosomes play in intercellular signaling upon fusion or uptake with a target cell, including immune system evasion, tumor growth and metastasis. To date, however, although exosomal membrane and cargo lipids are expected to play a pivotal role in exosome biogenesis and secretion, as well as in fusion or uptake and target cell functional response, the detailed characterization of cancer cell derived exosome lipids across a range of different cancers has not yet been broadly explored. Here, a simple and straightforward lipidome analysis strategy consisting of optimized sample extraction and novel sample derivatization techniques, coupled with high-resolution ‘shotgun’ mass spectrometry and ‘targeted’ tandem mass spectrometry methods, is demonstrated for the rapid identification of >520 individual lipids in 36 lipid classes and sub classes from exosomes secreted by the colorectal cancer cell line, LIM1215. Relative quantification and comparison of exosome versus cellular lipid profiles reveals significant enrichment of certain lipid classes, as well as substantial lipid subclass remodeling and changes in abundance of individual lipids, including sphingolipids, sterol lipids, glycerolipids and glycerophospholipids, and particularly plasmalogen- and alkyl ether-containing glycerophospholipids. This analysis strategy therefore provides a platform for comprehensive lipidome profiling across a wide range of cancer cell or tissue derived exosomes, that will facilitate subsequent functional studies aimed at elucidating the role of specific cellular or exosome lipids in the onset and progression of colorectal cancer, or to identify specific lipid(s) that could serve as effective diagnostic or prognostic disease biomarkers.

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Section: Resultsmentioning

confidence: 99%

Rapid and comprehensive ‘shotgun’ lipidome profiling of colorectal cancer cell derived exosomes

Lydic

Townsend

Adda

et al. 2015

Methods

167

184

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“…Several articles had shown that different exosomes derived from a variety of cells contained different components, for example heat shock proteins, annexin, lipids, and so on [28–30]. Phuyal S et al had reported that an increase in cellular ether lipids (including PCs) was associated with changes in the release and composition of exosomes in PC-3 cells [31]. The ePCs belong to subclasses of PCs, and ePCs activate Pl-3-kinase and may participate in mitogenic responses [32].…”

Section: Discussionmentioning

confidence: 99%

Plasma lipidomics profiling identified lipid biomarkers in distinguishing early-stage breast cancer from benign lesions

et al. 2016

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BackgroundBreast cancer is very common and highly fatal in women. Current non-invasive detection methods like mammograms are unsatisfactory. Lipidomics, a promising detection method, may serve as a novel prognostic approach for breast cancer in high-risk patients.ResultsAccording the predictive model, the combination of 15 lipid species had high diagnostic value. In the training set, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the combination of these 15 lipid species were 83.3%, 92.7%, 89.7%, and 87.9%, respectively. The AUC in the training set was 0.926 (95% CI 0.869-0.982). Similar results were found in the validation set, with the sensitivity, specificity, PPV and NPV at 81.0%, 94.5%, 91.9%, and 86.7%, respectively. The AUC was 0.938 (95% CI 0.889-0.986) in the validation set.MethodsUsing triple quadrupole liquid chromatography electrospray ionization tandem mass spectrometry, this study was to detect global lipid profiling of a total of 194 plasma samples from 84 patients with early-stage breast cancer (stage 0–II) and 110 patients with benign breast disease included in a training set and a validation set. A binary logistic regression was used to build a predictive model for evaluating the lipid species as potential biomarkers in the diagnosis of breast cancer.ConclusionThe combination of these 15 lipid species as a panel could be used as plasma biomarkers for the diagnosis of breast cancer.

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“…Although their precise role in cancer pathogenicity is unclear, ether lipids are important for the organization of detergent-resistant membrane microdomains [2]. Ether lipids may also be required for the assembly and release of exosomes, 40–100-nm vesicles secreted by cells, which may be involved in cell–cell communication and promoting cancer metastasis [67]. …”

Section: Peroxisomal Dysfunction In Disease Developmentmentioning

confidence: 99%

Peroxisomal Dysfunction in Age-Related Diseases

Cipolla

Lodhi

2017

Trends in Endocrinology & Metabolism

139

119

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Peroxisomes carry out many key functions related to lipid and reactive oxygen species (ROS) metabolism. The fundamental importance of peroxisomes for health in humans is underscored by the existence of devastating genetic disorders caused by impaired peroxisomal function or lack of peroxisomes. Emerging studies suggest that peroxisomal function may also be altered with aging and contribute to the pathogenesis of a variety of diseases, including diabetes and its related complications, neurodegenerative disorders, and cancer. With increasing evidence connecting peroxisomal dysfunction to the pathogenesis of these acquired diseases, the possibility of targeting peroxisomal function in disease prevention or treatment becomes intriguing. Here, we review recent developments in understanding the pathophysiological implications of peroxisomal dysfunctions outside the context of inherited peroxisomal disorders.

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The Ether Lipid Precursor Hexadecylglycerol Stimulates the Release and Changes the Composition of Exosomes Derived from PC-3 Cells

Cited by 117 publications

References 53 publications

Rapid and comprehensive ‘shotgun’ lipidome profiling of colorectal cancer cell derived exosomes

Rapid and comprehensive ‘shotgun’ lipidome profiling of colorectal cancer cell derived exosomes

Plasma lipidomics profiling identified lipid biomarkers in distinguishing early-stage breast cancer from benign lesions

Peroxisomal Dysfunction in Age-Related Diseases

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