121 research outputs found

    In vivo inhibition of c-MYC in myeloid cells impairs tumor-associated macrophage maturation and pro-tumoral activities

    Get PDF
    Although tumor-associated macrophages (TAMs) are involved in tumor growth and metastasis, the mechanisms controlling their pro-tumoral activities remain largely unknown. The transcription factor c-MYC has been recently shown to regulate in vitro human macrophage polarization and be expressed in macrophages infiltrating human tumors. In this study, we exploited the predominant expression of LysM in myeloid cells to generate c-Myc(fl/fl) LysM(cre/+) mice, which lack c-Myc in macrophages, to investigate the role of macrophage c-MYC expression in cancer. Under steady-state conditions, immune system parameters in c-Myc(fl/fl) LysM(cre/+) mice appeared normal, including the abundance of different subsets of bone marrow hematopoietic stem cells, precursors and circulating cells, macrophage density, and immune organ structure. In a model of melanoma, however, TAMs lacking c-Myc displayed a delay in maturation and showed an attenuation of pro-tumoral functions (e.g., reduced expression of VEGF, MMP9, and HIF1α) that was associated with impaired tissue remodeling and angiogenesis and limited tumor growth in c-Myc(fl/fl) LysM(cre/+) mice. Macrophage c-Myc deletion also diminished fibrosarcoma growth. These data identify c-Myc as a positive regulator of the pro-tumoral program of TAMs and suggest c-Myc inactivation as an attractive target for anti-cancer therapy

    Scientists’ Warning to Humanity: Rapid degradation of the world\u27s large lakes

    Get PDF
    Large lakes of the world are habitats for diverse species, including endemic taxa, and are valuable resources that provide humanity with many ecosystem services. They are also sentinels of global and local change, and recent studies in limnology and paleolimnology have demonstrated disturbing evidence of their collective degradation in terms of depletion of resources (water and food), rapid warming and loss of ice, destruction of habitats and ecosystems, loss of species, and accelerating pollution. Large lakes are particularly exposed to anthropogenic and climatic stressors. The Second Warning to Humanity provides a framework to assess the dangers now threatening the world\u27s large lake ecosystems and to evaluate pathways of sustainable development that are more respectful of their ongoing provision of services. Here we review current and emerging threats to the large lakes of the world, including iconic examples of lake management failures and successes, from which we identify priorities and approaches for future conservation efforts. The review underscores the extent of lake resource degradation, which is a result of cumulative perturbation through time by long-term human impacts combined with other emerging stressors. Decades of degradation of large lakes have resulted in major challenges for restoration and management and a legacy of ecological and economic costs for future generations. Large lakes will require more intense conservation efforts in a warmer, increasingly populated world to achieve sustainable, high-quality waters. This Warning to Humanity is also an opportunity to highlight the value of a long-term lake observatory network to monitor and report on environmental changes in large lake ecosystems
    corecore