Malignant features of minipig melanomas prior to spontaneous regression

Autor: Héloïse Débare, Fany Blanc, Guillaume Piton, Jean-Jacques Leplat, Silvia Vincent-Naulleau, Julie Rivière, Marthe Vilotte, Sylvain Marthey, Jérôme Lecardonnel, Jean-Luc Coville, Jordi Estellé, Andrea Rau, Emmanuelle Bourneuf, Giorgia Egidy
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Scientific Reports, Vol 14, Iss 1, Pp 1-14 (2024)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-024-59741-w
Popis: Abstract In MeLiM minipigs, melanomas develop around birth, can metastasize, and have histopathologic characteristics similar to humans. Interestingly, MeLiM melanomas eventually regress. This favorable outcome raises the question of their malignancy, which we investigated. We clinically followed tens of tumors from onset to first signs of regression. Transcriptome analysis revealed an enrichment of all cancer hallmarks in melanomas, although no activating or suppressing somatic mutation were found in common driver genes. Analysis of tumor cell genomes revealed high mutation rates without UV signature. Canonical proliferative, survival and angiogenic pathways were detected in MeLiM tumor cells all along progression stages. Functionally, we show that MeLiM melanoma cells are capable to grow in immunocompromised mice, with serial passages and for a longer time than in MeLiM pigs. Pigs set in place an immune response during progression with dense infiltration by myeloid cells while melanoma cells are deficient in B2M expression. To conclude, our data on MeLiM melanomas reveal several malignancy characteristics. The combination of these features with the successful spontaneous regression of these tumors make it an outstanding model to study an efficient anti-tumor immune response.
Databáze: Directory of Open Access Journals
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