The Role of PPAR?/? in Melanoma Metastasis.

ABSTRACT: BACKGROUND:Peroxisome proliferator?activated receptor (PPAR) ?/?, 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, PPAR?/? has been linked to carcinogenesis and was reported to inhibit melanoma cell proliferation, anchorage-dependent clonogenicity and ectopic xenograft tumorigenicity. However, PPAR?/?'s role in tumour progression and metastasis remains controversial. METHODS:In the present studies, the consequence of PPAR?/? inhibition either by global genetic deletion or by a specific PPAR?/? antagonist, 10h, on malignant transformation of melanoma cells and melanoma metastasis was examined using both in vitro and in vivo models. RESULTS: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 Ppar?/?-/- 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 Ppar?/?-/- mice as demonstrated in the same animal model. CONCLUSION:These results indicated a protective role of PPAR?/? in melanoma progression and metastasis.

SUBMITTER: Lim JCW 

PROVIDER: S-EPMC6213649 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature