G-CSF and G-CSFR are highly expressed in human gastric and colon cancers and promote carcinoma cell proliferation and migration

K. T. Morris, H. Khan, A. Ahmad, L. L. Weston, R. A. Nofchissey, Iryna Pinchuk, E. J. Beswick

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1211-1220
Number of pages10
JournalBritish Journal of Cancer
Volume110
Issue number5
DOIs
StatePublished - Mar 4 2014

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Granulocyte Colony-Stimulating Factor Receptors
Granulocyte Colony-Stimulating Factor
Colonic Neoplasms
Stomach Neoplasms
Cell Movement
Cell Proliferation
Carcinoma
Neoplasms
Stomach
Colon
Myofibroblasts
Myeloid Progenitor Cells
Colorectal Neoplasms
Intercellular Signaling Peptides and Proteins
Stem Cells
Phosphorylation
Cytokines

Keywords

  • Colon cancer
  • G-CSF
  • G-CSFR
  • Gastric cancer
  • Stem cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Morris, K. T., Khan, H., Ahmad, A., Weston, L. L., Nofchissey, R. A., Pinchuk, I., & Beswick, E. J. (2014). G-CSF and G-CSFR are highly expressed in human gastric and colon cancers and promote carcinoma cell proliferation and migration. British Journal of Cancer, 110(5), 1211-1220. https://doi.org/10.1038/bjc.2013.822

G-CSF and G-CSFR are highly expressed in human gastric and colon cancers and promote carcinoma cell proliferation and migration. / Morris, K. T.; Khan, H.; Ahmad, A.; Weston, L. L.; Nofchissey, R. A.; Pinchuk, Iryna; Beswick, E. J.

In: British Journal of Cancer, Vol. 110, No. 5, 04.03.2014, p. 1211-1220.

Research output: Contribution to journalArticle

Morris, KT, Khan, H, Ahmad, A, Weston, LL, Nofchissey, RA, Pinchuk, I & Beswick, EJ 2014, 'G-CSF and G-CSFR are highly expressed in human gastric and colon cancers and promote carcinoma cell proliferation and migration', British Journal of Cancer, vol. 110, no. 5, pp. 1211-1220. https://doi.org/10.1038/bjc.2013.822
Morris, K. T. ; Khan, H. ; Ahmad, A. ; Weston, L. L. ; Nofchissey, R. A. ; Pinchuk, Iryna ; Beswick, E. J. / G-CSF and G-CSFR are highly expressed in human gastric and colon cancers and promote carcinoma cell proliferation and migration. In: British Journal of Cancer. 2014 ; Vol. 110, No. 5. pp. 1211-1220.
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AU - Ahmad, A.

AU - Weston, L. L.

AU - Nofchissey, R. A.

AU - Pinchuk, Iryna

AU - Beswick, E. J.

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AB - 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.

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