Expression of granulocyte‐colony‐stimulating factor and its receptor in human Ewing sarcoma cells and patient tumor specimens

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. Cancer 2007. © 2007 American Cancer Society.

Priming of neutrophils toward NETosis promotes tumor growth

“…14 Interestingly, LLC tumor, Ewing sarcomas and pancreatic carcinomas have all been reported to express G-CSF. 7,18,19 Moreover, pancreatic carcinomas are associated with myeloid systemic and intratumoral accumulations. 20 In cancer patients, increase in neutrophil count and elevated blood G-CSF have been frequently observed and associated with poor outcome.…”

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

“…Besides stimulating neutrophils, G-CSF may stimulate non-hematopoietic malignant tumor cell growth in an autocrine fashion [173,194]. G-CSF receptor (G-CSFR) expression has been observed in bladder cancer cells [195], ovarian cancer [196], colorectal cancer [197] and Ewing sarcoma [198]. G-CSF administration increased tumor growth of Erwin sarcoma [198], and must therefore be carefully considered before use for stimulating neutrophil recruitment following chemotherapy.…”

“…G-CSF is often secreted by tumor cells [26,174,189,190,194,198,276,[352][353][354][355][356][357][358][359] and is preferentially observed in dedifferentiated or poorly differentiated tumors [360,361,354,190]. Elevated G-CSF blood concentrations in cancer patients have been associated with poor clinical outcome [174,194,198,276,352,355,356].…”

Leiomyosarcoma in the humerus with leukocytosis and elevation of serum G-CSF

“…Some reports have indicated that G-CSF can support the growth of osteosarcoma and Ewing sarcoma [12,13]. In contrast, G-CSF expression was not found to be an adverse prognostic factor in ovarian carcinomas [14].…”