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

Arantza Perez-Valle,Patricia Aspichueta,Olatz Fresnedo,María Dolores Boyano,Egoitz Astigarraga,Gabriel Barreda-Gómez,José A Fernández,Aintzane Asumendi,Begoña Ochoa,Beatriz Abad-García

doi:10.3390/ijms222112061

Abstract

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.

Highlights

The melanocyte lipid landscape was further analyzed by assessing whether the variations in species abundance affect the relative expression of the total lipid classes
Literature search failed to to retrieve lipidomic data from the most popular, the Clark model, considers the melanoma development to be a linear melanocytes isolated from clinically diagnosed benign nevus
We identified significant changes to 53 lipid species that tell us more about how melanoma grows and spreads and how nevus melanocytes do not share the perturbations in the lipid metabolism of melanoma cells

Summary

Introduction

Melanoma is regarded as the deadliest form of skin cancer, arising after the malignant transformation of neural crest-derived melanocytes in the epidermis of the skin [1] The transformation of these cells is due to a plethora of molecular alterations (reviewed in [2]), including activating mutations in the proto-oncogene kinase BRAF. Alterations in lipid metabolism and the development of a lipogenic phenotype have emerged as early biochemical hallmarks of cancer cells [11,12,13,14,15,16,17,18] In this regard, studies assessing the metabolic behavior of melanoma have demonstrated that such phenotypic plasticity confers adaptive advantages favoring proliferation and survival [4,19,20]. While the de novo biosynthesis of fatty acids (FA) is mild in normal adult tissues, the tumorigenesisassociated increase in lipid production enables cells to create a strategically structured new biomass [12,13], helping them better handle changing environmental conditions [3]

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Conclusion