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CHRONIC SKIN INFLAMMATION PROMOTES MELANOMA AGGRESSIVENESS IN ZEBRAFISH
Autores:
ELENA GOMEZ ABENZA
, CHIARA GABELLINI, MARINA MIONE, LEONARD I. ZON,
MARIA LUISA CAYUELA FUENTES
,
VICTORIANO MULERO MÉNDEZ
,
Grupos de investigación:
[GI/IMIB/C060/2011] Inmunidad, inflamación y cáncer
[GI/IMIB/C003/2011] Cirugía digestiva, endocrina y trasplante de órganos abdominales
Comunicación:
Antecedentes:
Inflammation and cancer have a profound yet ambiguous relationship. Chronic inflammation exerts protumorigenic effects but inflammatory cells may also kill tumor cells and immunosuppression increases cancer risk.
Métodos:
We evaluated the impact of inflammation in promoting melanoma in vivo using a spontaneous model of melanoma in zebrafish (kita: eGFP-HRAS-V12), in combination with spint1a (hai1a) deficiency, which promotes chronic skin inflammation. We also performed allotransplant assays in both larvae and adult zebrafish previously irradiated to evaluate the melanoma aggressiveness in vivo. Molecular characterization of tumour samples was performed by RNA-Seq.
Resultados:
We found that skin inflammation increases oncogenic transformation and accelerates the onset of oncogenic HRAS driven melanoma. The allotransplant assays showed a key role of inflammatory cells in enhancing melanoma aggressiveness. Transcriptomic studies revealed that inflammation promotes IFN? signaling, glutathione-dependent antioxidant responses, leukotriene biosynthesis and myeloid infiltration.
Conclusiones:
Our data suggest that chronic skin inflammation might results in a more aggressive melanoma phenotype. The identification of genes involved in the response of melanoma cells to the inflammatory microenvironment may help in the identification of novel targets and anti-inflammatory-based therapies to counteract melanoma aggressiveness.
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