Relevance of CCL3/CCR5 axis in oral carcinogenesis
Carregando...
Data
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Federal de Minas Gerais
Descrição
Tipo
Artigo de periódico
Título alternativo
Primeiro orientador
Membros da banca
Resumo
The chemokine CCL3 is a chemotactic cytokine crucial for inflammatory cell recruitment in homeostatic and pathological conditions. CCL3 might stimulate cancer progression by promoting leukocyte accumulation, angiogenesis and tumour growth. The expression of CCL3 and its receptors CCR1 and CCR5 was demonstrated in oral squamous cell carcinoma (OSCC), but their role was not defined. Here, the functions of CCL3 were assessed using a model of chemically induced tongue carcinogenesis with 4-nitroquinoline-1-oxide (4NQO). Lineages of OSCC were used to analyse the effects of CCL3 in vitro. The 4NQO-induced lesions exhibited increased expression of CCL3, CCR1 and CCR5. CCL3-/- and CCR5-/- mice presented reduced incidence of tongue tumours compared to wild-type (WT) and CCR1-/- mice. Consistently, attenuated cytomorphological atypia and reduced cell proliferation were observed in lesions of CCL3-/- and CCR5-/- mice. OSCC from CCL3-/- mice exhibited lower infiltration of eosinophils and reduced expression of Egf, Fgf1, Tgf-β1, Vegfa, Vegfb, Itga-4, Vtn, Mmp-1a, Mmp-2 and Mmp-9 than WT mice. In vitro, CCL3 induced invasion and production of CCL5, IL-6, MMP -2, -8, -9. Blockage of CCL3 in vitro using α-CCL3 or Evasin-1 (a CCL3-binding protein) impaired tumour cell invasion. In conclusion, CCL3/CCR5 axis has pro-tumourigenic effects in oral carcinogenesis. The induction of inflammatory and angiogenic pathways and eosinophils recruitment appear to be the underlying mechanism explaining these effects. These data reveal potential protective effects of CCL3 blockade in oral cancer.
Abstract
Assunto
Chemokine CCL3, Receptors, CCR1, Receptors, CCR5, Squamous cell carcinoma of head and neck, Chemokines, Angiogenesis, Evaluation study, Eosinophils, Carcinogenesis, Epidermal Growth Factor, Fibroblast Growth Factor 1, Transforming Growth Factor beta1, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor B, Genes, Proteins, Interleukin-6, Matrix Metalloproteinase 2, Matrix Metalloproteinase 1, Matrix Metalloproteinase 8, Matrix Metalloproteinase 9
Palavras-chave
Chemokines, CCL3, CCR1, CCR5, OSCC
Citação
Curso
Endereço externo
https://www.oncotarget.com/article/16882/text/