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

JULIETA MARINO; VERÓNICA A. FURMENTO; ELSA ZOTTA; LEONOR P. ROGUIN

CANCER BIOLOGY & THERAPY

Landes Bioscience

Lugar: Philidelphia, PA; Año: 2009 vol. 8 p. 1740 - 1746

1538-4047

The aim of the present study was to evaluate the in vivoeffect of granulocyte colony-stimulating factor (G-CSF) onLM3 murine mammary adenocarcinoma cells subcutaneouslyimplanted in Balb/c mice as experimental models.We showed that the peritumoral administration of 100μg/kg of G-CSF diminished tumor progression, while nocytokine effect on LM3 cell proliferation was observed in vitro.Histological examination of G-CSF-treated tumors revealedinfiltration of neutrophils and mononuclear cells. Apoptoticcells were identified by TUNEL assays. Western blot analysisof tumor lysates showed that G-CSF treatment increased theamount of Fas-L, TRAIL and Bax proteins, whereas decreasedthe expression of procaspase 3 and Bcl-2. In addition, cytokinearrays showed an increment in the amount of IL-12, IL-13 andTNFalpha. Our results suggest that the presence of G-CSF withintumor microenvironment would induce an immune responsewhich eliminates tumor cells by apoptosis. Both death receptorand mitochondrial pathways would be involved in LM3 tumorcell death. We believe that the final local G-CSF concentrationat the tumor site and each particular type of tumor should becarefully taken into account in order to evaluate the effect of thecytokine on tumor progression.