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

Data de publicação:

Autores da FMUP

  • Raquel Ângela Silva Soares Lino

    Autor

Participantes de fora da FMUP

  • Fonseca, M
  • Coelho, P

Unidades de investigação

Abstract

Obesity 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. C57B16/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 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. Copyright

Dados da publicação

ISSN/ISSNe:
1473-5636, 0960-8931

Melanoma Research  Lippincott Williams and Wilkins Ltd.

Tipo:
Article
Páginas:
515-525
Link para outro recurso:
www.scopus.com

Citações Recebidas na Scopus: 2

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Keywords

  • Animals; Apoptosis; Cell Line, Tumor; Diet, High-Fat; Fibroblast Growth Factors; Humans; Lung Neoplasms; Melanoma; Mice; Mice, Obese; Neoplasm Metastasis; Prognosis; Skin Neoplasms; fibroblast growth factor; fibroblast growth factor 21; adverse event; animal; apoptosis; complication; human; lipid diet; lung tumor; melanoma; metabolism; metastasis; mouse; mouse mutant; prognosis; skin tumor; tumor cell line

Proyectos asociados

Effects of Xanthohumol on Metabolic Syndrome Progression (XAN4Health) - NCT03561116

Investigador Principal: Raquel Ângela Silva Soares Lino

Ensaio Clínico Académico (XAN4Health) . TA XAN . 2019

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