Objective: We previously described a cancer stem cell population in neuroblastoma (NB) based on the expression of granulocyte colony stimulating factor (G-CSF) receptor. In our studies, the ligand G-CSF leads to increased primary tumor growth and metastasis in an orthotopic mouse model. Therefore, we hypothesize that G-CSF leads to increased metastatic disease and decreased survival in a mouse model of minimal residual disease.
Methods: The human NB cell line, CHLA-255, was injected into the kidneys of NSG mice, and the primary tumor resected on day 7. Mice were randomized into the following groups: control (n=4), G-CSF (n=6), chemotherapy (etoposide)(n=6), chemo followed by G-CSF (n=7). The G-CSF alone and chemo alone groups were treated for 2 weeks starting day 10. The combination group underwent 2 weeks of chemotherapy followed by 2 weeks of G-CSF. Bioluminescent imaging was performed to assess metastatic disease. Survival was analyzed by log-rank test.
Results: Four weeks after tumor resection, there was decreased burden of metastatic residual disease in each treatment group, compared to control (p<0.01). No difference was observed between the chemo alone and chemo+G-CSF groups (p=0.82). Similarly, survival was significantly prolonged in each treatment group, compared to control (p<0.02). Moreover, no difference in survival was observed when chemotherapy was followed by G-CSF treatment (p=0.98)
Conclusion: Our results show that G-CSF does not increase metastatic disease nor does it worsen survival in our metastatic tumor resection model of neuroblastoma. Further studies are warranted to elucidate the role and safety of G-CSF in patients with high-risk NB.
