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Although these processes largely depend on the lipid-based cell membrane scaffold, our understanding of the melanoma lipid phenotype lags behind most other aspects of this tumor cell. Here, we examined a panel of normal human epidermal and nevus melanocytes and primary and metastatic melanoma cell lines to determine whether distinctive cell-intrinsic lipidomes can discern non-neoplastic from neoplastic melanocytes and define their metastatic potential. Lipidome profiles were obtained by UHPLC-ESI mass-spectrometry, and differences in the signatures were analyzed by multivariate statistical analyses. Significant and highly specific changes in more than 30 lipid species were annotated in the initiation of melanoma, whereas less numerous changes were associated with melanoma progression and the non-malignant transformation of nevus melanocytes. Notably, the \u201cmalignancy lipid signature\u201d features marked drops in pivotal membrane lipids, like sphingomyelins, and aberrant elevation of ether-type lipids and phosphatidylglycerol and phosphatidylinositol variants, suggesting a previously undefined remodeling of sphingolipid and glycerophospholipid metabolism. Besides broadening the molecular definition of this neoplasm, the different lipid profiles identified may help improve the clinical diagnosis\/prognosis and facilitate therapeutic interventions for cutaneous melanoma.<\/jats:p>","DOI":"10.3390\/ijms222112061","type":"journal-article","created":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T08:05:16Z","timestamp":1636358716000},"page":"12061","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["A UHPLC-Mass Spectrometry View of Human Melanocytic Cells Uncovers Potential Lipid Biomarkers of Melanoma"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3108-4978","authenticated-orcid":false,"given":"Arantza","family":"Perez-Valle","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country UPV\/EHU, 48940 Leioa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6945-5730","authenticated-orcid":false,"given":"Beatriz","family":"Abad-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Central Analysis Service, Faculty of Science and Technology, University of the Basque Country UPV\/EHU, 48940 Leioa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1172-1423","authenticated-orcid":false,"given":"Olatz","family":"Fresnedo","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country UPV\/EHU, 48940 Leioa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8330-1567","authenticated-orcid":false,"given":"Gabriel","family":"Barreda-G\u00f3mez","sequence":"additional","affiliation":[{"name":"IMG Pharma Biotech S.L., Bizkaia Technological Park, 48160 Derio, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3553-1755","authenticated-orcid":false,"given":"Patricia","family":"Aspichueta","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country UPV\/EHU, 48940 Leioa, Spain"},{"name":"Biocruces-Bizkaia Research Institute, Cruces University Hospital, 48903 Barakaldo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2156-2323","authenticated-orcid":false,"given":"Aintzane","family":"Asumendi","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country UPV\/EHU, 48940 Leioa, Spain"},{"name":"Biocruces-Bizkaia Research Institute, Cruces University Hospital, 48903 Barakaldo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0338-5554","authenticated-orcid":false,"given":"Egoitz","family":"Astigarraga","sequence":"additional","affiliation":[{"name":"IMG Pharma Biotech S.L., Bizkaia Technological Park, 48160 Derio, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 A.","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Department of Physical Chemistry, Faculty of Science and Technology, University of the Basque Country UPV\/EHU, 48940 Leioa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6051-1054","authenticated-orcid":false,"given":"Mar\u00eda Dolores","family":"Boyano","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country UPV\/EHU, 48940 Leioa, Spain"},{"name":"Biocruces-Bizkaia Research Institute, Cruces University Hospital, 48903 Barakaldo, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1580-7160","authenticated-orcid":false,"given":"Bego\u00f1a","family":"Ochoa","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country UPV\/EHU, 48940 Leioa, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"aad2197","DOI":"10.1126\/science.aad2197","article-title":"A Zebrafish Melanoma Model Reveals Emergence of Neural Crest Identity during Melanoma Initiation","volume":"351","author":"Kaufman","year":"2016","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"vi8","DOI":"10.1093\/annonc\/mdp251","article-title":"Biomarkers in Melanoma","volume":"20","author":"Gogas","year":"2009","journal-title":"Ann. 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