Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros








Base de dados
Intervalo de ano de publicação
1.
Elife ; 52016 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-27823583

RESUMO

The tumor microenvironment is a critical modulator of carcinogenesis; however, in many tumor types, the influence of the stroma during preneoplastic stages is unknown. Here we explored the relationship between pre-tumor cells and their surrounding stroma in malignant progression of the cerebellar tumor medulloblastoma (MB). We show that activation of the vascular regulatory signalling axis mediated by Norrin (an atypical Wnt)/Frizzled4 (Fzd4) inhibits MB initiation in the Ptch+/- mouse model. Loss of Norrin/Fzd4-mediated signalling in endothelial cells, either genetically or by short-term blockade, increases the frequency of pre-tumor lesions and creates a tumor-permissive microenvironment at the earliest, preneoplastic stages of MB. This pro-tumor stroma, characterized by angiogenic remodelling, is associated with an accelerated transition from preneoplasia to malignancy. These data expose a stromal component that regulates the earliest stages of tumorigenesis in the cerebellum, and a novel role for the Norrin/Fzd4 axis as an endogenous anti-tumor signal in the preneoplastic niche.


Assuntos
Carcinogênese , Proteínas do Olho/metabolismo , Receptores Frizzled/metabolismo , Meduloblastoma/fisiopatologia , Proteínas do Tecido Nervoso/metabolismo , Transdução de Sinais , Animais , Modelos Animais de Doenças , Regulação da Expressão Gênica , Camundongos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA