Purpose: G-CSF (Granulocyte Colony-Stimulating Factor) is commonly used in cancer patients to ameliorate neutropenia and to prevent severe infections. Many recent preclinical studies reveal tumor promoting and stem cell mobilizing effect of G-CSF. Because of severe toxicity, it is suggested that G-CSF should be avoided during concomitant chemoradiotherapy. The safety of G-CSF in cancer treatment especially during radiotherapy should be re-evaluated. Materials and Methods: To evaluate tumor promoting and mobilizing effect of G-CSF with or without local radiation, tumor growth delay and lung colony assay of B16F10 melanoma and Lewis lung carcinoma cells were established. Direct effect of G-CSF on cells was evaluated by in vitro proliferating, wound-healing and trans-well migration assay. In vivo effect of G-CSF was evaluated by histology studies. The role of bone marrow (BM) stem cells in tumor growth and metastasis was studied by subcutaneous tumor implant in chimeric mice, established 4 weeks after BM transplantation from green fluorescence protein (GFP) transgenic mice. GFP labeled BM cells in tumors and organs were evaluated by flow cytometry and immunohistochemistry. Results: High dose long duration of G-CSF enhanced local tumor growth with increased tumor vessel density in both tumor models. The promoting effect was suppressed when G-CSF was given along with radiation. G-CSF did not enhance tumor or stromal cell proliferation directly but recruited BM cells to tumor site. After local radiation, the amount of BM cells recruited by G-CSF to tumor site decreased. This phenomenon is associated with decreased microvessel density in tumors. The incidence of lung metastasis was increased by both local radiation and G-CSF treatment. But there was no additive effect between G-CSF and radiation on tumor metastasis. G-CSF enhanced tumor cell motility and increased BM cell recruitment to normal lung. When combined with local radiation, tumor cell motility was not further enhanced, neither the amount of BM cell mobilized to lung. Conclusion: Administration of G-CSF is safe during local radiotherapy. Concomitant G-CSF and radiation may not promote local tumor growth or distant metastasis.
Date:
2009-05
Relation:
Cancer Research. 2009 May;69(9):Abstract number 711.
