G-CSF is a key modulator of MDSC and could be a potential therapeutic target in colitis-associated colorectal cancers.
10.1007/s13238-015-0237-2
- Author:
Wenbin LI
1
;
Xinghua ZHANG
1
;
Yongkang CHEN
1
;
Yibin XIE
2
;
Jiancheng LIU
1
;
Qiang FENG
2
;
Yi WANG
3
;
Wei YUAN
4
;
Jie MA
5
Author Information
1. State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
2. Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
3. Department of VIP, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
4. State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China. yuanwei7568@163.com.
5. State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China. majiecicams@163.com.
- Publication Type:Journal Article
- Keywords:
cancer;
granulocyte colony-stimulating factor;
inflammation;
myeloid derived suppressor cells
- MeSH:
Animals;
Carcinogenesis;
Colitis;
complications;
Colorectal Neoplasms;
complications;
drug therapy;
immunology;
metabolism;
Female;
Gene Expression Regulation, Neoplastic;
Granulocyte Colony-Stimulating Factor;
genetics;
metabolism;
Immunotherapy;
Mice;
Molecular Targeted Therapy;
Myeloid Cells;
immunology;
metabolism;
pathology
- From:
Protein & Cell
2016;7(2):130-140
- CountryChina
- Language:English
-
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.
