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

Abstract

In vivo antitumor effect of G-CSFThe 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 μg/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 TNFα. 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.

The role of G-CSF in the treatment of advanced tumors

“…15,17 Conversely, in their study Marino et al found that the histological examination of tumor slices from treated and non-treated mice did not reveal any difference in tumor vascularization. 14 In addition, they did not find a change in the expression levels of an angiogenic factor, such as VEGF, either by cytokine array or when tumor lysates were examined by western blot with an specific anti-VEGF antibody. The relationship between G-CSF and tumor cells is very complex, however; since, for example, some tumors themselves can produce G-CSF and/or GM-CSF.…”

“…In this issue of Cancer Biology & Therapy, Marino et al investigate the potential relationships between G-CSF and tumor progression. 14 This study was carried out in vivo using a syngeneic BALB/c mouse mammary tumor model. The authors demonstrated that the in vivo peritumoral administration of G-CSF effectively inhibited LM3 murine mammary adenocarcinoma growth by activating the migration of neutrophils and mononuclear cells, which would induce an apoptotic effect responsible for tumor cell death.…”

Decomposition of Variation of Mixed Variables by a Latent Mixed Gaussian Copula Model

“…CSF3 and FLT3LG play synergistic roles in the physiological steady state for maintenance of neutrophil and dendritic cell populations. TNFSF10 is critical in promoting infectioninduced inflammation, and experiments showed that G-CSF treatment increased the amount of TNFSF10 and the infiltration of neutrophils and mononuclear cells (Marino et al, 2009). CCL5 plays an important role in sustaining CD8 cytotoxic T cell responses and CCL23 is highly chemotactic for monocytes.…”

Leveling Up the Controversial Role of Neutrophils in Cancer: When the Complexity Becomes Entangled

“…The activated neutrophils kill the tumor cells by a combined effect of reactive oxygen and nitrogen species, such as hydrogen peroxide (H 2 O 2 ), superoxide anion (O 2 − · ), hypochlorous acid (HOCl) and nitric oxide radical (NO · ), together with FasL and TRAIL [ 53 , 60 , 75 , 118 , 167 , 168 , 202 , 219 , 221 , 222 , 223 , 224 , 225 ] ( Figure 3 ). Recently, human neutrophil elastase was found to kill tumor cells by proteolytically liberating the CD95 death domain, which interacts with histone H1 isoforms [ 262 ].…”