Abstract
Looking beyond tumor angiogenesis, the past decade has witnessed a fundamental change of paradigm with the discovery that the vascular endothelium does not just respond to exogenous cytokines, but exerts active "angiocrine" gatekeeper roles, controlling their microenvironment in an instructive manner. While vascular niches host disseminated cancer cells and promote their stemness, endothelial cell-derived angiocrine signals orchestrate a favorable immune milieu to facilitate metastatic growth. Here, we discuss recent advances in the field of tumor microenvironment research and propose angiocrine signals as promising targets of future mechanism-driven antimetastatic therapies, which may prove useful to synergistically combine with chemotherapy and immunotherapy.
©2019 American Association for Cancer Research.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inhibitors / pharmacology*
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Angiogenesis Inhibitors / therapeutic use
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Animals
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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Carcinogenesis / drug effects*
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Carcinogenesis / pathology
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Disease Models, Animal
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Disease Progression
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Drug Evaluation, Preclinical
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Endothelial Cells / pathology
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Endothelium, Vascular / cytology
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / pathology*
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Humans
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Neoplasm Metastasis / pathology
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Neoplasm Metastasis / prevention & control*
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Neoplasms / blood supply
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Neoplasms / drug therapy*
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Neoplasms / pathology
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Neoplastic Cells, Circulating / pathology
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Neovascularization, Pathologic / drug therapy
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Neovascularization, Pathologic / pathology
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Receptors, Vascular Endothelial Growth Factor / metabolism
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Signal Transduction / drug effects
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Tumor Microenvironment / drug effects
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Vascular Endothelial Growth Factor A / metabolism
Substances
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Angiogenesis Inhibitors
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Vascular Endothelial Growth Factor A
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Receptors, Vascular Endothelial Growth Factor