Paclitaxel  treatment and PC1/3 knockdown in macrophages is a promising anti-glioma strategy as revealed by proteomics and cytotoxicity studies.

We report here that such a treatment of PC1/3 KD macrophages drove to the overexpression of proteins mainly involved in cytoskeleton rearrangement. In support of this finding, we found that these cells exhibited a Ca2+ increase after Paclitaxel treatment. This is indicative of a possible depolymerization of microtubules and may therefore reflect an activation of inflammatory pathways in macrophages. In such a way, we found that PC1/3 KD macrophages displayed a repression of the anti-inflammatory pathway STAT3 and secreted more pro-inflammatory cytokines. Extracellular vesicles isolated from these PC1/3 KD cells inhibited glioma growth. Finally, the supernatant collected from the co-culture between glioma cells and PC1/3 KD macrophages contained more anti-tumoral factors. These findings unravel the potential value of a new therapeutic strategy combining Paclitaxel and PC1/3 inhibition to switch macrophages toward an anti-tumoral immunophenotype.
PMID: 29531019 [PubMed - as supplied by publisher]

Source: Molecular and Cellular Proteomics : MCP - March 12, 2018 Category: Molecular Biology Authors: Duhamel M, Rose M, Rodet F, Murgoci AN, Zografidou L, Régnier-Vigouroux A, Vanden Abeele F, Kobeissy F, Nataf S, Pays L, Wisztorski M, Cizkova D, Fournier I, Salzet M Tags: Mol Cell Proteomics Source Type: research