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Expression of granulocyte-colony-stimulating factor and its receptor in human Ewing sarcoma cells and patient tumor specimens
Potential consequences of granulocyte-colony-stimulating factor administration
Version of Record online: 10 AUG 2007
Copyright © 2007 American Cancer Society
Volume 110, Issue 7, pages 1568–1577, 1 October 2007
How to Cite
Morales-Arias, J., Meyers, P. A., Bolontrade, M. F., Rodriguez, N., Zhou, Z., Reddy, K., Chou, A. J., Koshkina, N. V. and Kleinerman, E. S. (2007), Expression of granulocyte-colony-stimulating factor and its receptor in human Ewing sarcoma cells and patient tumor specimens. Cancer, 110: 1568–1577. doi: 10.1002/cncr.22964
- Issue online: 14 SEP 2007
- Version of Record online: 10 AUG 2007
- Manuscript Accepted: 24 MAY 2007
- Manuscript Revised: 19 MAY 2007
- Manuscript Received: 14 FEB 2007
- Ewing sarcoma;
- granulocyte-colony-stimulating factor (G-CSF);
- granulocyte-colony-stimulating factor receptor (G-CSFR);
Ewing sarcoma (ES) is a highly vascular malignancy. It has been demonstrated that both angiogenesis and vasculogenesis contribute to the growth of ES tumors. Granulocyte-colony-stimulating factor (G-CSF), a cytokine known to stimulate bone marrow (BM) stem cell production and angiogenesis, is routinely administered to ES patients after chemotherapy. Whether ES cells and patient tumor samples express G-CSF and its receptor (G-CSFR) and whether treatment with this factor enhances tumor growth was examined.
Human ES cell lines were analyzed for expression of G-CSF and G-CSFR in vitro and in vivo. Sixty-eight paraffin-embedded and 15 frozen tumor specimens from patients with ES were also evaluated for the presence of G-CSF and G-CSFR. The in vivo effect of G-CSF on angiogenesis and BM cell migration was determined. Using a TC/7-1 human ES mouse model, the effect of G-CSF administration on ES tumors was investigated.
G-CSF and G-CSFR protein and RNA expression was identified in all ES cell lines and patient samples analyzed. In addition, G-CSF was found to stimulate angiogenesis and BM cell migration in vivo. Tumor growth was found to be significantly increased in mice treated with G-CSF. The average tumor volume for the group treated with G-CSF was 1218 mm3 compared with 577 mm3 for the control group (P = .006).
The findings that ES cells and patient tumors expressed both G-CSF and its receptor in vitro and in vivo and that the administration of G-CSF promoted tumor growth in vivo suggest that the potential consequences of G-CSF administration should be investigated further. Cancer 2007. © 2007 American Cancer Society.