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

Jaime Morales-Arias, Paul A. Meyers, Marcela F. Bolontrade, Nidra Rodriguez, Zhichao Zhou, Krishna Reddy, Alexander J. Chou, Nadezhda V. Koshkina, Eugenie S. Kleinerman

Research output: Contribution to journalArticle

28 Scopus citations

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 mm3 compared with 577 mm3 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.

Original languageEnglish (US)
Pages (from-to)1568-1577
Number of pages10
JournalCancer
Volume110
Issue number7
DOIs
StatePublished - Oct 1 2007
Externally publishedYes

Keywords

  • Angiogenesis
  • Ewing sarcoma
  • Granulocyte-colony-stimulating factor (G-CSF)
  • Granulocyte-colony-stimulating factor receptor (G-CSFR)
  • Vasculogenesis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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