The bidirectional crosstalk between metastatic uveal melanoma cells and hepatic stellate cells engenders an inflammatory microenvironment.
Exp Eye Res
; 181: 213-222, 2019 04.
Article
en En
| MEDLINE
| ID: mdl-30771295
ABSTRACT
Uveal melanoma is the most common primary ocular neoplasm in adults. It is peculiar for its hematogenous dissemination and its high propensity to spread to the liver. Current treatments rarely prolong patient survival. We hypothesized that metastatic uveal melanoma cells modulate the function of surrounding hepatic stellate cells to facilitate their own growth and survival. This study was conducted to investigate the role of the hepatic microenvironment on uveal melanoma aggressiveness. We demonstrated that the paracrine signaling of surrounding hepatic stellate cells have more transcriptional impact on metastatic uveal melanoma cells. Upregulated transcripts were linked to inflammation and included several interleukins. The uveal melanoma-stellate cell crosstalk induced as well the expression of transmembrane integrins. In addition, the interleukin-6 receptor inhibitor Tocilizumab did not reduce the growth of uveal melanoma cells. Our results provide evidence that inflammatory mediators are key players in the homing of uveal melanoma cells to the liver. The bidirectional crosstalk between uveal melanoma cells and hepatic stellate cells involved pro-fibrogenic interleukins. The inflammatory characteristics of the metastatic microenvironment might offer relevant therapeutic opportunities in uveal melanoma.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Neoplasias de la Úvea
/
ARN Neoplásico
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Citocinas
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Células Estrelladas Hepáticas
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Inflamación
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Neoplasias Hepáticas
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Melanoma
Límite:
Humans
Idioma:
En
Revista:
Exp Eye Res
Año:
2019
Tipo del documento:
Article
País de afiliación:
Francia