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
in English
| WPRIM
| ID: wpr-757155
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Colorectal Neoplasms
/
Gene Expression Regulation, Neoplastic
/
Granulocyte Colony-Stimulating Factor
/
Colitis
/
Myeloid Cells
/
Drug Therapy
/
Allergy and Immunology
/
Molecular Targeted Therapy
/
Carcinogenesis
Type of study:
Prognostic study
Limits:
Animals
Language:
English
Journal:
Protein & Cell
Year:
2016
Type:
Article
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