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TNF-Î± as a key player in Melanoma cell aggressiveness

ABSTRACT: Purpose. Aggressiveness is a crucial issue related to cutaneous melanoma malignancy and its high metastatic potential. Aim of this work is to identify new pathways or molecules controlling melanoma cell aggressiveness. Proliferation, migration and invasion capability under serum stimulation were analyzed in 12 human metastatic melanoma cell lines to identify the most aggressive ones as a model. The most proliferating/invading (defines as the most aggressive) A375 cell line was compared to the less aggressive one, Sk mel 28 by means of different approaches: 1) transcriptomic analysis by ILLUMINA platform; 2) proteomic study through LC-MS/MS analysis; 3) multiplexed assay to measure secretion of cytokines in conditioned media bioinformatic analysis was then carried out. Two groups of cells significantly differing in aggressiveness were identified and 2 cell lines, namely A375 and SK-Mel-28 were selected as model of the most and the less aggressive phenotype, respectively. A multi-omic analysis of several experimental datasets derived from transcriptomic, proteomic (mass spectrometric) and cytokinomic data was then carried out via Ingenuity Pathway Analysis (IPA) software. Analysis of upstream regulators and network analysis, indicated that the expression of tumor necrosis factor (TNF) were significantly differently expressed and functioning. The involvement of these pathways was confirmed by functional validation studies as zymography and proliferation studies and the most significantly upregulated pathway (TNF-alfa) was tested. Five melanoma cell lines with different MAGS were treated with an anti-TNFÎ± monoclonal antibody and the most aggressive ones were highly significantly affected.

ORGANISM(S): Homo sapiens

SUBMITTER: Giovanni Nassa

PROVIDER: E-MTAB-4212 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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