Peritumoral administration of granulocyte colony-stimulating factor induces an apoptotic response on a murine mammary adenocarcinoma

MARINO V.J.; FURMENTO V.A.; ZOTTA E; ROGUIN, L. P

CANCER BIOLOGY & THERAPY

Landes Bioscience

Lugar: Austin. Texas; Año: 2009 vol. 8 p. 1737 - 1743

1538-4047

The aim of the present study was to evaluate the in vivo effect of granulocyte colony-stimulating factor on LM3 murine mammary adenocarcinoma cells subcutaneously implanted in Balb/c mice as experimental models. We showed that the peritumoral administration of G-CSF diminished tumor progression, while no cytokine effect on LM3 cell proliferation was observed in vitro. Histological examination of G-CSF-treated tumors revealed infiltration of neutrophils and mononuclear cells. Apoptotic cells were identified by TUNEL assays. Western blot analysis of tumor lysates showed that G-CSF treatment increased the amount of Fas-L, TRAIL and Bax proteins, whereas decreased the expression of procaspase 3 and Bcl-2. In addition, cytokine arrays showed an increment in the amount of IL-12, IL-13 and TNF-alpha. Our results suggest that the presence of G-CSF within tumor microenvironmentinduce an immune response which eliminates tumor cells by apoptosis. Both death receptor and mitochondrial pathways would be involved in LM3 tumor cell death. We believe that the final local G-CSF concentration at the tumor site and each particular type of tumor should be carefully taken into account in order to evaluate the effect of the cytokine on tumor progression.