G-CSF is a key modulator of MDSC and could be a potential therapeutic target in colitis-associated colorectal cancers
Protein & Cell
; (12): 130-140, 2016.
Article
em En
| WPRIM
| ID: wpr-757155
Biblioteca responsável:
WPRO
ABSTRACT
Granulocyte colony-stimulating factor (G-CSF) is an essential regulator of neutrophil trafficking and is highly expressed in multiple tumors. Myeloid derived suppressor cells (MDSCs) promote neoplastic progression through multiple mechanisms by immune suppression. Despite the findings of G-CSF function in colon cancer progression, the precise mechanism of G-CSF on MDSCs regulation and its blockade effects on tumor growth remains a worthy area of investigation. In this study we observed an overexpression of G-CSF in a mouse colitis-associated cancer (CAC) model, which was consistent with the accumulation of MDSCs in mouse colon tissues. Further in vitro studies demonstrated that G-CSF could promote MDSCs survival and activation through signal transducer and activator of transcription 3 (STAT3) signaling pathway. Moreover, compared with isotype control, anti-G-CSF mAb treatment demonstrated reduced MDSC accumulation, which led to a marked decrease in neoplasm size and number in mice. Our results indicated that G-CSF is a critical regulating molecule in the migration, proliferation and function maintenance of MDSCs, which could be a potential therapeutic target for colitis-associated cancer.
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Texto completo:
1
Índice:
WPRIM
Assunto principal:
Patologia
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Neoplasias Colorretais
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Regulação Neoplásica da Expressão Gênica
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Fator Estimulador de Colônias de Granulócitos
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Colite
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Células Mieloides
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Tratamento Farmacológico
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Alergia e Imunologia
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Terapia de Alvo Molecular
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Carcinogênese
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Protein & Cell
Ano de publicação:
2016
Tipo de documento:
Article