G-CSF and G-CSFR are highly expressed in human gastric and colon cancers and promote carcinoma cell proliferation and migration.
BACKGROUND
Granulocyte colony-stimulating factor (G-CSF) is a pro-inflammatory cytokine that stimulates myeloid stem cell maturation, proliferation, and migration into circulation. Despite being a known growth factor, the impact of G-CSF on solid tumours has not been well examined. G-CSF receptor (G-CSFR) is expressed by some tumours, and thus the aim of this study was to examine the expression and impact of G-CSF and G-CSFR on gastrointestinal tumours.


METHODS
In this study, G-CSF expression was examined in human gastric and colon tumours and by tumour-derived stromal myofibroblasts and carcinoma cells. G-CSFR expression was examined on carcinoma cells isolated from human tissues. The effects of G-CSF on gastric and colon carcinoma cell proliferation, migration, and signalling were examined.


RESULTS
G-CSFR was highly expressed in 90% of human gastric and colon carcinomas. G-CSF was also found to be highly produced by stromal myofibroblasts and carcinoma cells. Exposure of carcinoma cells to G-CSF led to increased proliferation and migration, and expansion of a sub-population of carcinoma cells expressing stem-like markers. These processes were dependent on ERK1/2 and RSK1 phosphorylation.


CONCLUSIONS
These data suggest that the G-CSF/R axis promotes gastric and colorectal cancer development and suggest they are potential tumour targets.
Department of Surgery, University of New Mexico, Albuquerque, NM, USA.
K T
KT
Morris
Department of Surgery, University of New Mexico, Albuquerque, NM, USA.
H
H
Khan
Department of Surgery, University of New Mexico, Albuquerque, NM, USA.
A
A
Ahmad
Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, NM, USA.
L L
LL
Weston
Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, NM, USA.
R A
RA
Nofchissey
Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA.
I V
IV
Pinchuk
Department of Molecular Genetics and Microbiology, University of New Mexico, Albuquerque, NM, USA.
E J
EJ
Beswick
D018938:Caco-2 Cells; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D058628:Myofibroblasts / Q000473:pathology; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics*; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology
D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor; C069329:RPS6KA1 protein, human; D038744:Ribosomal Protein S6 Kinases, 90-kDa