A UHPLC-Mass Spectrometry View of Human Melanocytic Cells Uncovers Potential Lipid Biomarkers of Melanoma

Melanoma is the deadliest form of skin cancer due to its ability to colonize distant sites and initiate metastasis. 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....

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Autores: Pérez Valle, Arantza, Abad García, Beatriz, Fresnedo Aranguren, María Olatz, Barreda Gómez, Gabriel, Aspichueta Celaá, Patricia, Asumendi Mallea, Aintzane, Astigarraga Arribas, Egoitz, Fernández González, José Andrés, Boyano López, María Dolores, Ochoa Olascoaga, Begoña
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/54068
Acceso en línea:http://hdl.handle.net/10810/54068
Access Level:acceso abierto
Palabra clave:lipid biomarker
lipid phenotype
human
melanoma
melanocyte
nevus melanocyte
sphingomyelin
plasmalogen
ether lipid
metastasis
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spelling A UHPLC-Mass Spectrometry View of Human Melanocytic Cells Uncovers Potential Lipid Biomarkers of MelanomaPérez Valle, ArantzaAbad García, BeatrizFresnedo Aranguren, María OlatzBarreda Gómez, GabrielAspichueta Celaá, PatriciaAsumendi Mallea, AintzaneAstigarraga Arribas, EgoitzFernández González, José AndrésBoyano López, María DoloresOchoa Olascoaga, Begoñalipid biomarkerlipid phenotypehumanmelanomamelanocytenevus melanocytesphingomyelinplasmalogenether lipidmetastasisMelanoma is the deadliest form of skin cancer due to its ability to colonize distant sites and initiate metastasis. 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 “malignancy lipid signature” 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.This research was funded in part by grants from the Ministry of Economy; Industry and Competitiveness (RTC-2015-3693-1); Ministry of Science and Innovation (RTI-2018-095134-B-I00); Basque Government (IT971-16; IT1162-19; KK2016-036; KK2017-041 and KK2018-00090) and UPV/EHU (GIU17/066).MDPI2021202120212021info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/54068reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoInglésinfo:eu-repo/grantAgreement/MINECO/RTC-2015-3693-1/info:eu-repo/grantAgreement/MINECO/RTI-2018-095134-B-I00/https://www.mdpi.com/1422-0067/22/21/12061/htminfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/3.0/es/2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).oai:addi.ehu.eus:10810/540682026-06-18T09:23:17Z
dc.title.none.fl_str_mv A UHPLC-Mass Spectrometry View of Human Melanocytic Cells Uncovers Potential Lipid Biomarkers of Melanoma
title A UHPLC-Mass Spectrometry View of Human Melanocytic Cells Uncovers Potential Lipid Biomarkers of Melanoma
spellingShingle A UHPLC-Mass Spectrometry View of Human Melanocytic Cells Uncovers Potential Lipid Biomarkers of Melanoma
Pérez Valle, Arantza
lipid biomarker
lipid phenotype
human
melanoma
melanocyte
nevus melanocyte
sphingomyelin
plasmalogen
ether lipid
metastasis
title_short A UHPLC-Mass Spectrometry View of Human Melanocytic Cells Uncovers Potential Lipid Biomarkers of Melanoma
title_full A UHPLC-Mass Spectrometry View of Human Melanocytic Cells Uncovers Potential Lipid Biomarkers of Melanoma
title_fullStr A UHPLC-Mass Spectrometry View of Human Melanocytic Cells Uncovers Potential Lipid Biomarkers of Melanoma
title_full_unstemmed A UHPLC-Mass Spectrometry View of Human Melanocytic Cells Uncovers Potential Lipid Biomarkers of Melanoma
title_sort A UHPLC-Mass Spectrometry View of Human Melanocytic Cells Uncovers Potential Lipid Biomarkers of Melanoma
dc.creator.none.fl_str_mv Pérez Valle, Arantza
Abad García, Beatriz
Fresnedo Aranguren, María Olatz
Barreda Gómez, Gabriel
Aspichueta Celaá, Patricia
Asumendi Mallea, Aintzane
Astigarraga Arribas, Egoitz
Fernández González, José Andrés
Boyano López, María Dolores
Ochoa Olascoaga, Begoña
author Pérez Valle, Arantza
author_facet Pérez Valle, Arantza
Abad García, Beatriz
Fresnedo Aranguren, María Olatz
Barreda Gómez, Gabriel
Aspichueta Celaá, Patricia
Asumendi Mallea, Aintzane
Astigarraga Arribas, Egoitz
Fernández González, José Andrés
Boyano López, María Dolores
Ochoa Olascoaga, Begoña
author_role author
author2 Abad García, Beatriz
Fresnedo Aranguren, María Olatz
Barreda Gómez, Gabriel
Aspichueta Celaá, Patricia
Asumendi Mallea, Aintzane
Astigarraga Arribas, Egoitz
Fernández González, José Andrés
Boyano López, María Dolores
Ochoa Olascoaga, Begoña
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv lipid biomarker
lipid phenotype
human
melanoma
melanocyte
nevus melanocyte
sphingomyelin
plasmalogen
ether lipid
metastasis
topic lipid biomarker
lipid phenotype
human
melanoma
melanocyte
nevus melanocyte
sphingomyelin
plasmalogen
ether lipid
metastasis
description Melanoma is the deadliest form of skin cancer due to its ability to colonize distant sites and initiate metastasis. 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 “malignancy lipid signature” 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.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/54068
url http://hdl.handle.net/10810/54068
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MINECO/RTC-2015-3693-1/
info:eu-repo/grantAgreement/MINECO/RTI-2018-095134-B-I00/
https://www.mdpi.com/1422-0067/22/21/12061/htm
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/3.0/es/
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
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