Abstract
BACKGROUND.
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.
METHODS.
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.
RESULTS.
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 mm^3^ compared with 577 mm^3^ for the control group (P = .006).
CONCLUSIONS.
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.