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  • American Association for the Advancement of Science (AAAS)  (2)
Type of Medium
Publisher
  • American Association for the Advancement of Science (AAAS)  (2)
Language
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  • 1
    In: Science Signaling, American Association for the Advancement of Science (AAAS), Vol. 3, No. 107 ( 2010-02-02)
    Abstract: The family of bone morphogenetic proteins (BMPs) comprises approximately 30 secreted cytokines that signal through transmembrane serine/threonine kinase receptors. The BMP signaling pathways are fine-tuned on multiple levels: Extracellular antagonists modify ligand activity; several co-receptors enhance or inhibit downstream signaling events through multiple mechanisms; and intracellular molecules further regulate the signaling outcome and mediate crosstalk with other pathways. BMPs affect structures and processes throughout the entire body, ranging from embryonic patterning and development through stem cells and their niches, to tissue homeostasis and regeneration. This comprehensive involvement in various tissues had not been expected by Marshall Urist, who initially discovered the ability of an unknown factor in bone to induce bone growth in muscle and subsequently suggested the name “bone morphogenetic protein.” Today, recombinant BMPs are used in clinical practice for the treatment of bone and kidney disorders, and new genetically modified BMPs are emerging as promising tools in regenerative medicine and tissue engineering. Clearly, the functions of BMPs within the body are more versatile than initially suspected. To discuss modern trends in BMP signaling, leaders in the field met for the First International BMP Workshop in Berlin in September 2009. Here, we summarize new insights on the roles of BMPs in various tissues and highlight recent findings in cell, structural, and developmental biology as well as the therapeutic potential of BMPs. Finally, we conclude that BMPs today deserve to be called body morphogenetic proteins.
    Type of Medium: Online Resource
    ISSN: 1945-0877 , 1937-9145
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2010
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  • 2
    Online Resource
    Online Resource
    American Association for the Advancement of Science (AAAS) ; 2019
    In:  Science Immunology Vol. 4, No. 39 ( 2019-09-13)
    In: Science Immunology, American Association for the Advancement of Science (AAAS), Vol. 4, No. 39 ( 2019-09-13)
    Abstract: Immune evasion in the tumor microenvironment (TME) is a crucial barrier for effective cancer therapy, and plasticity of innate immune cells may contribute to failures of targeted immunotherapies. Here, we show that rivaroxaban, a direct inhibitor of activated coagulation factor X (FX), promotes antitumor immunity by enhancing infiltration of dendritic cells and cytotoxic T cells at the tumor site. Profiling FX expression in the TME identifies monocytes and macrophages as crucial sources of extravascular FX. By generating mice with immune cells lacking the ability to produce FX, we show that myeloid cell–derived FX plays a pivotal role in promoting tumor immune evasion. In mouse models of cancer, we report that the efficacy of rivaroxaban is comparable with anti–programmed cell death ligand 1 (PD-L1) therapy and that rivaroxaban synergizes with anti–PD-L1 in improving antitumor immunity. Mechanistically, we demonstrate that FXa promotes immune evasion by signaling through protease-activated receptor 2 and that rivaroxaban specifically targets this cell-autonomous signaling pathway to reprogram tumor-associated macrophages. Collectively, our results have uncovered the importance of FX produced in the TME as a regulator of immune cell activation and suggest translational potential of direct oral anticoagulants to remove persisting roadblocks for immunotherapy and provide extravascular benefits in other diseases.
    Type of Medium: Online Resource
    ISSN: 2470-9468
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2019
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