title: G-CSF is a key modulator of MDSC and could be a potential therapeutic target in colitis-associated colorectal cancers.
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.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Li
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
authors.forename: Xinghua
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
authors.forename: Yongkang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
authors.forename: Yibin
authors.initials: Y
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
authors.forename: Jiancheng
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Feng
authors.affiliation: Department of VIP, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China. yuanwei7568@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Yuan
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 100021, China. majiecicams@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D003092:Colitis / Q000150:complications*; D015179:Colorectal Neoplasms / Q000150:complications* / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D007167:Immunotherapy; D051379:Mice; D058990:Molecular Targeted Therapy; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D016179:Granulocyte Colony-Stimulating Factor
keywords: cancer; granulocyte colony-stimulating factor; inflammation; myeloid derived suppressor cells