Peritumoral administration of granulocyte colony-stimulating factor induces an apoptotic response on a murine mammary adenocarcinoma.
The aim of the present study was to evaluate the in vivo effect of granulocyte colony-stimulating factor (G-CSF) on LM3 murine mammary adenocarcinoma cells subcutaneously implanted in Balb/c mice as experimental models. We showed that the peritumoral administration of 100 microg/kg 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 TNFalpha. Our results suggest that the presence of G-CSF within tumor microenvironment would induce 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.
Marino
Julieta
J
Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina.
Furmento
Verónica A
VA
Zotta
Elsa
E
Roguin
Leonor P
LP
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D016466:CHO Cells; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D018664:Interleukin-12 / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D053222:Fas Ligand Protein; D018793:Interleukin-13; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505654:Tnfsf10 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D016179:Granulocyte Colony-Stimulating Factor; D018664:Interleukin-12; D053148:Caspase 3