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Lower melanoma pulmonary metastatic burden in obese mice: role of FGF-21

2021-08-17Journal article Restricted access
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dc.contributor.authorFonseca, Magda
dc.contributor.authorSoares, Raquel
dc.contributor.authorCoelho, Pedro
dc.date.accessioned2021-11-24T16:40:54Z
dc.date.available2021-11-24T16:40:54Z
dc.date.issued2021-08-17
dc.description.abstractObesity is a risk factor for malignant melanoma. The lungs are main target organs for metastization and their immune response is a key modulator of this mechanism. The concept that the metastatic potential of some types of cancer is reduced or inhibited by obesity, known as the obesity paradox, drives major concerns on the prognosis of metastasized patients. The aim of this study was to investigate how high-fat diet (HFD)-induced obesity affects melanoma metastization. C57Bl6/J mice were fed with HFD or standard diet for 180 days and inoculated intravenously with B16F10 melanoma cells. Upon 21 days of inoculation, lung tissue of overweight and lean mice was assessed for histology and immunohistochemistry assays. Adipokine antibody arrays were performed in mice serum. In vitro RAW 264.7 macrophage cultures were established and incubated with FGF-21 and/or lipopolysaccharide (LPS). Conditioned media was added to B16F10 cells for viability quantification. HFD-fed mice presented a reduced number of metastases with lower proliferative rates. The high content of inflammatory foci observed in noninoculated obese mice was significantly decreased upon B16F10 inoculation, concurrent with a slight fibrosis reduction. Plasma levels of fibroblast growth factor-21 (FGF-21), an endocrine regulator, were elevated in noninoculated HFD mice and the expression of FGF receptor 1 (FGFR-1) was significantly upregulated after inoculation. FGF-21 reduced melanoma viability in LPS-stimulated macrophages. Altogether, these findings suggest that higher amounts of FGF-21 are able to counterbalance the proinflammatory effects associated with obesity, protecting the lungs from melanoma metastization.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationFonseca, M., Soares, R., & Coelho, P. (2021). Lower melanoma pulmonary metastatic burden in obese mice: role of FGF-21. Melanoma Research, 31(6), 515-525. https://doi.org/10.1097/cmr.0000000000000781pt_PT
dc.identifier.doi10.1097/CMR.0000000000000781pt_PT
dc.identifier.issn0960-8931
dc.identifier.urihttp://hdl.handle.net/10400.22/18945
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWolters Kluwerpt_PT
dc.relation.publisherversionhttps://journals.lww.com/melanomaresearch/Abstract/2021/12000/Lower_melanoma_pulmonary_metastatic_burden_in.3.aspxpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectFGF-21pt_PT
dc.subjectObesity paradoxpt_PT
dc.subjectMelanomapt_PT
dc.subjectTumor dormancypt_PT
dc.titleLower melanoma pulmonary metastatic burden in obese mice: role of FGF-21pt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage525pt_PT
oaire.citation.startPage515pt_PT
oaire.citation.titleMelanoma Researchpt_PT
oaire.citation.volume31pt_PT
person.familyNameCoelho
person.givenNamePedro
person.identifier.ciencia-idBE18-3DB2-8D79
person.identifier.orcid0000-0002-2343-1108
person.identifier.ridAAZ-9239-2020
person.identifier.scopus-author-id57214054449
rcaap.rightsclosedAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationeb030614-4140-437b-8ac3-f59c52566ecf
relation.isAuthorOfPublication.latestForDiscoveryeb030614-4140-437b-8ac3-f59c52566ecf

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