G-CSF is a key modulator of MDSC and could be a potential therapeutic target in colitisassociated colorectal cancers
Received date: 29 Sep 2015
Accepted date: 30 Nov 2015
Published date: 13 Mar 2016
Copyright
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.
Wenbin Li , Xinghua Zhang , Yongkang Chen , Yibin Xie , Jiancheng Liu , Qiang Feng , Yi Wang , Wei Yuan , Jie Ma . G-CSF is a key modulator of MDSC and could be a potential therapeutic target in colitisassociated colorectal cancers[J]. Protein & Cell, 2016 , 7(2) : 130 -140 . DOI: 10.1007/s13238-015-0237-2
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