The Role of PPARβ/δ in Melanoma Metastasis
BACKGROUND: 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.
METHODS: 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.
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 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.
CONCLUSION: These results indicated a protective role of PPARβ/δ in melanoma progression and metastasis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:19 |
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| Enthalten in: |
International journal of molecular sciences - 19(2018), 10 vom: 20. Sept. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lim, Jonathan Chee Woei [VerfasserIn] |
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| Links: |
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| Themen: |
EMT |
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| Anmerkungen: |
Date Completed 28.01.2019 Date Revised 28.01.2019 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/ijms19102860 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM288778618 |
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| 100 | 1 | |a Lim, Jonathan Chee Woei |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The Role of PPARβ/δ in Melanoma Metastasis |
| 264 | 1 | |c 2018 | |
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| 500 | |a Date Completed 28.01.2019 | ||
| 500 | |a Date Revised 28.01.2019 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: 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 | ||
| 520 | |a METHODS: 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 | ||
| 520 | |a 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 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 | ||
| 520 | |a CONCLUSION: These results indicated a protective role of PPARβ/δ in melanoma progression and metastasis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a EMT | |
| 650 | 4 | |a invasion | |
| 650 | 4 | |a melanoma | |
| 650 | 4 | |a metastasis | |
| 650 | 4 | |a migration | |
| 650 | 4 | |a peroxisome proliferator–activated receptor β/δ | |
| 650 | 7 | |a PPAR delta |2 NLM | |
| 650 | 7 | |a PPAR-beta |2 NLM | |
| 700 | 1 | |a Kwan, Yuet Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Michelle Siying |e verfasserin |4 aut | |
| 700 | 1 | |a Teo, Melissa Hui Yen |e verfasserin |4 aut | |
| 700 | 1 | |a Chiba, Shunsuke |e verfasserin |4 aut | |
| 700 | 1 | |a Wahli, Walter |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiaomeng |e verfasserin |4 aut | |
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