CONICET | Buscador de Institutos y Recursos Humanos

Leukocyte-specific protein 1 (LSP1) is a 52kDa cytoplasmic F-actinbinding phosphoprotein expressed in all human and murine leukocytes as well as in endothelial cells. This protein in known as animportant regulator of actin cytoskeleton remodeling. LSP1 polymorphismsor downregulation are considered risk factors for some typesof cancer.We previously shown that B16-OVA melanoma in Lsp1-/- mice growssignificantly faster and bigger than in wild type (WT) controls. Also,tumors harvested from Lsp1-/- mice show a lower frequency of totalinfiltrating leukocytes compared to WT mice. Furthermore, there isa reduced extravasation efficiency of Lsp1-/- leukocytes into tumor,combined with a defective CD8+ T cell priming in Lsp1-/- tumor dLN.We continued this study by comparing the cytokine milieu in melanomatumors in Lsp1-/- vs WT mice. For that, 1.105 B16-OVA melanomacells were implanted in both animal groups and on day 16 tumorswere harvested. Aproximately 70 mg tumor/mouse was digestedusing T-PER? Tissue Protein Extraction Reagent added with proteaseinhibitor. Tumor-cytokine content was determined by a multiplexcommercial assay using fluorescence?encoded beads that allowssimultaneous quantification of 13 mouse cytokines including IL-1α,IL-1β, IL-6, IL-10, IL-12p70, IL-17A, IL-23, IL-27, MCP-1, IFN-β,IFN-γ, TNF-α and GM-CSF. We found that tumors in Lsp1-/- micehave significantly higher levels of IL-1β, IL-10, IL-27, IL-17A and IL-23 (p<0.01) as well as higher levels of TNF-α, IL-12p70, IFN-β andGM-CSF (p<0.001) than WT mice. However, tumor extracts containedsimilar levels of IL-1α, INF-γ, MCP-1 and IL-6. Sumarizing,the tumoral milieu in Lsp1-/- mice has increased levels of cytokinesthat can act as angiogenesis promoters, favoring tumoral growthand chronic inflammation, as well as cytokines involved in promotingDC activation.

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