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.
|Number of pages||10|
|Journal||British Journal of Cancer|
|State||Published - Mar 4 2014|
Bibliographical noteFunding Information:
This work was supported by grants from the American Cancer Society (RSG-10-159-01-LIB) and (IRG-92-024) and National Institutes of Health 8UL1TR000041, The University of New Mexico Clinical and Translational Science Center. We would like to thank Dr Laurie Hudson, Department of Pharmaceutical Sciences at the University of New Mexico, for reviewing the article and providing helpful advice. We would also like to acknowledge Legacy Research Tumor Bank for generously supplying tumour samples.
- Colon cancer
- Gastric cancer
- Stem cells
ASJC Scopus subject areas
- Cancer Research