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Extracellular vesicles released by fibroblasts undergoing H-Ras induced senescence show changes in lipid profile

Author

Listed:
  • Sandra Buratta
  • Lorena Urbanelli
  • Krizia Sagini
  • Stefano Giovagnoli
  • Silvia Caponi
  • Daniele Fioretto
  • Nico Mitro
  • Donatella Caruso
  • Carla Emiliani

Abstract

Cells release extracellular vesicles (EVs) in their environment and cellular lipids play an important role in their formation, secretion and uptake. Besides, there is also evidence that EV transferred lipids impact on recipient’s cell signaling. Cellular senescence is characterized by a state of permanent proliferation arrest and represents a barrier towards the development of neoplastic lesions. A peculiar feature of senescence is the release of many soluble factors, the so-called Senescence-Associated Secretory Phenotype, which play a key role in triggering paracrine senescence signals. Recently, evidences have suggested that this phenotype includes not only soluble factors, but also EVs. To identify lipid signatures associated with H-Ras-induced senescence in EVs, we expressed active H-Ras (H-RasV12) in human fibroblasts and investigated how it affects EV release and lipid composition. An enrichment of hydroxylated sphingomyelin, lyso- and ether-linked phospholipids and specific H-Ras-induced senescence signatures, e.g. sphingomyelin, lysophosphatidic acid and sulfatides, were found in EVs compared to cells. Furthermore, H-RasV12 expression in fibroblasts was associated with higher levels of tetraspanins involved in vesicle formation.

Suggested Citation

  • Sandra Buratta & Lorena Urbanelli & Krizia Sagini & Stefano Giovagnoli & Silvia Caponi & Daniele Fioretto & Nico Mitro & Donatella Caruso & Carla Emiliani, 2017. "Extracellular vesicles released by fibroblasts undergoing H-Ras induced senescence show changes in lipid profile," PLOS ONE, Public Library of Science, vol. 12(11), pages 1-23, November.
    • Handle: RePEc:plo:pone00:0188840
    DOI: 10.1371/journal.pone.0188840
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    1. Raffaella Di Micco & Marzia Fumagalli & Angelo Cicalese & Sara Piccinin & Patrizia Gasparini & Chiara Luise & Catherine Schurra & Massimiliano Garre’ & Paolo Giovanni Nuciforo & Aaron Bensimon & Rober, 2006. "Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication," Nature, Nature, vol. 444(7119), pages 638-642, November.
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