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20 septembre 2018
- doi: 10.3390/ijms19102860
- issn: 1422-0067
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info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms19102860
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info:eu-repo/semantics/altIdentifier/pmid/30241392
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info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_08607DDF85B09
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Melanocytic tumor Malignant melanomaCiter ce document
JCW Lim et al., « The Role of PPARβ/δ in Melanoma Metastasis. », Serveur académique Lausannois, ID : 10.3390/ijms19102860
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Résumé
Peroxisome proliferator⁻activated receptor (PPAR) β/δ, a ligand-activated transcription factor, is involved in diverse biological processes including cell proliferation, cell differentiation, inflammation and energy homeostasis. Besides its well-established roles in metabolic disorders, PPARβ/δ has been linked to carcinogenesis and was reported to inhibit melanoma cell proliferation, anchorage-dependent clonogenicity and ectopic xenograft tumorigenicity. However, PPARβ/δ's role in tumour progression and metastasis remains controversial. In the present studies, the consequence of PPARβ/δ inhibition either by global genetic deletion or by a specific PPARβ/δ antagonist, 10h, on malignant transformation of melanoma cells and melanoma metastasis was examined using both in vitro and in vivo models. Our study showed that 10h promotes epithelial-mesenchymal transition (EMT), migration, adhesion, invasion and trans-endothelial migration of mouse melanoma B16/F10 cells. We further demonstrated an increased tumour cell extravasation in the lungs of wild-type mice subjected to 10h treatment and in Pparβ/δ -/- mice in an experimental mouse model of blood-borne pulmonary metastasis by tail vein injection. This observation was further supported by an increased tumour burden in the lungs of Pparβ/δ -/- mice as demonstrated in the same animal model. These results indicated a protective role of PPARβ/δ in melanoma progression and metastasis.