New panel of biomarkers to discriminate between amelanotic and melanotic metastatic melanoma

Abstract

Melanoma is a form of skin cancer that can rapidly invade distant organs. A distinctive feature of melanomas is their pigmentation status, as melanin is present in most skin melanomas, whilst many metastatic tumors could become amelanotic. Besides the obvious malfunction of the key genes of the melanin pathway, the amelanotic tumors could bear a characteristic molecular signature accounting for their aggressivity. Using mass spectrometry-based proteomics we report here a distinctive panel of biomarkers for amelanotic aggressive melanoma that differ from the less invasive pigmented cells. The developed method allows the label-free quantification of proteins identified by LC-MS/MS analysis. We found a set of proteins comprising AHNAK, MYOF, ANXA1, CAPN2, ASPH, EPHA2, THBS1, TGM2, ACTN4 along with proteins involved in cell adhesion/migration (integrins, PLEC, FSCN1, FN1) that are highly expressed in amelanotic melanoma. Accompanying the down regulation of pigmentation specific proteins such as tyrosinase and TYRP1, these biomarkers are highly specific for a type of highly invasive melanoma. Interestingly, the LC-MS/MS proteomics analysis in hypoxia revealed that the abundance of this specific set of proteins found in normoxia was rather unaltered in these conditions. These biomarkers could therefore predict a metastatic behaviour for the amelanotic cells in the early stages of the tumor development and thus serve in melanoma prognostic. Applying this algorithm to related databases including melanoma samples published by independent laboratories/public databases we confirm the specificity of the newly found signatures. Overall, we begin to unravel the molecular alterations in the amelanotic melanoma and how basic proteomics offers insights into how to assess the clinical, pathological and misdiagnosis differences between the main subtypes of melanoma.

NPC1 plays a role in the trafficking of specific cargo to melanosomes

“…S1 B ). This could suggest that in cells producing more pigment there is a more stringent requirement for NPC1 function, although other biomarkers are more relevant for pigmentation, as we recently reported ( 30 ). Co-immunoprecipitation studies using the NPC1 antibody revealed a possible direct interaction between TYR and NPC1 ( Fig.…”

Morin Hydrate Encapsulation and Release from Mesoporous Silica Nanoparticles for Melanoma Therapy

“…The cell lines A375 [ 23 , 54 , 86 , 87 ], MNT-1 [ 57 , 88 ] and SK-MEL-28 [ 89 , 90 ] have been extensively utilized as melanoma models in various studies. The A375 and SK-MEL-28 cell lines are non-pigmented (amelanotic), in contrast with MNT-1, which is highly pigmented [ 91 ]. The cytotoxic effects of morin hydrate (non-encapsulated, MH), MSNs (blank nanoparticles) and morin-loaded MSNs (MH-MSNs) against melanoma cell lines were evaluated using the MTT assay.…”

The Pro-Oncogenic Sphingolipid-Metabolizing Enzyme β-Galactosylceramidase Modulates the Proteomic Landscape in BRAF(V600E)-Mutated Human Melanoma Cells

“…Mass spectrometry (MS)-based proteomics has been emerging as a core technique for largescale protein characterization in cells and tissue samples by providing a qualitative and quantitative analysis of proteins produced under different physiological and pathological conditions, including cancer [ 2 ]. Recently, analysis of the proteome has been considered as a tool for the advancement of diagnostic and prognostic biomarkers in melanoma, as well as for the identification of biological pathways leading to melanoma progression [ 3 , 4 , 5 ].…”