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.
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.
Morales-Arias
Jaime
J
Division of Pediatrics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. jmorales@mdanderson.org
Meyers
Paul A
PA
Bolontrade
Marcela F
MF
Rodriguez
Nidra
N
Zhou
Zhichao
Z
Reddy
Krishna
K
Chou
Alexander J
AJ
Koshkina
Nadezhda V
NV
Kleinerman
Eugenie S
ES
D001859:Bone Neoplasms / Q000098:blood supply / Q000737:chemistry* / Q000473:pathology; D045744:Cell Line, Tumor; D002633:Chemotaxis; D015972:Gene Expression Regulation, Neoplastic; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D009389:Neovascularization, Pathologic; D012313:RNA / Q000032:analysis; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000032:analysis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012512:Sarcoma, Ewing / Q000098:blood supply / Q000737:chemistry* / Q000473:pathology
D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor; D012313:RNA