The tumor microenvironment Anderson, Nicole M.; Simon, M. Celeste
Current biology,
08/2020, Letnik:
30, Številka:
16
Journal Article
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A tumor is not simply a group of cancer cells, but rather a heterogeneous collection of infiltrating and resident host cells, secreted factors and extracellular matrix. Tumor cells stimulate ...significant molecular, cellular and physical changes within their host tissues to support tumor growth and progression. An emerging tumor microenvironment is a complex and continuously evolving entity. The composition of the tumor microenvironment varies between tumor types, but hallmark features include immune cells, stromal cells, blood vessels, and extracellular matrix. It is believed that the “tumor microenvironment is not just a silent bystander, but rather an active promoter of cancer progression” (Truffi et al., 2020). Early in tumor growth, a dynamic and reciprocal relationship develops between cancer cells and components of the tumor microenvironment that supports cancer cell survival, local invasion and metastatic dissemination. To overcome a hypoxic and acidic microenvironment, the tumor microenvironment coordinates a program that promotes angiogenesis to restore oxygen and nutrient supply and remove metabolic waste. Tumors become infiltrated with diverse adaptive and innate immune cells that can perform both pro- and anti- tumorigenic functions (Figure 1). An expanding literature on the tumor microenvironment has identified new targets within it for therapeutic intervention.
The tumor microenvironment is a complex entity. Here, Anderson and Simon introduce this complex collection of cells, metabolites and extracellular matrix, and the role it plays in cancer progression.
Iron is an essential micronutrient for microorganisms, plants, animals, and humans. However, iron overload can damage the organism through a variety of mechanisms, including the induction of cell ...death. Ferroptosis is defined as an iron-dependent form of regulated cell death caused by unrestricted lipid peroxidation and subsequent membrane damage. Ferroptosis can be triggered through either the extrinsic or the intrinsic pathway. The extrinsic pathway is initiated through the regulation of transporters (e.g., inhibition of the amino acid antiporter system xc
or activation of the iron transporters transferrin and lactotransferrin), whereas the intrinsic pathway is mainly induced by blocking the expression or activity of intracellular antioxidant enzymes, such as glutathione peroxidase 4 (GPX4). In addition to small-molecule compounds and drugs, certain stresses (e.g., high temperature, low temperature, hypoxia, and radiation) induce ferroptotic cell death. The abnormal regulation of this process, which is connected to protein degradation pathways, such as autophagy and the ubiquitin-proteasome system, is associated with various pathological conditions, including acute tissue damage, infection, cancer, and neurodegeneration. Here, we discuss the core process and regulation of ferroptosis in mammalian cells, as well as its therapeutic implications in disease.
Exosomes and ectosomes, two distinct types of extracellular vesicles generated by all types of cell, play key roles in intercellular communication. The formation of these vesicles depends on local ...microdomains assembled in endocytic membranes for exosomes and in the plasma membrane for ectosomes. These microdomains govern the accumulation of proteins and various types of RNA associated with their cytosolic surface, followed by membrane budding inward for exosome precursors and outward for ectosomes. A fraction of endocytic cisternae filled with vesicles — multivesicular bodies — are later destined to undergo regulated exocytosis, leading to the extracellular release of exosomes. In contrast, the regulated release of ectosomes follows promptly after their generation. These two types of vesicle differ in size — 50–150 nm for exosomes and 100–500 nm for ectosomes — and in the mechanisms of assembly, composition, and regulation of release, albeit only partially. For both exosomes and ectosomes, the surface and luminal cargoes are heterogeneous when comparing vesicles released by different cell types or by single cells in different functional states. Upon release, the two types of vesicle navigate through extracellular fluid for varying times and distances. Subsequently, they interact with recognized target cells and undergo fusion with endocytic or plasma membranes, followed by integration of vesicle membranes into their fusion membranes and discharge of luminal cargoes into the cytosol, resulting in changes to cellular physiology. After fusion, exosome/ectosome components can be reassembled in new vesicles that are then recycled to other cells, activating effector networks. Extracellular vesicles also play critical roles in brain and heart diseases and in cancer, and are useful as biomarkers and in the development of innovative therapeutic approaches.
In this review, Meldolesi focuses on the recent progress made by studies of the biology and physiology of extracellular vesicles and discusses the role of these vesicles in disease and their potential therapeutic applications.
Appropriation of fresh water to meet human needs is growing, and competition among users will intensify in a warmer and more crowded world. This essay explains why freshwater ecosystems are global ...hotspots of biological richness, despite a panoply of interacting threats that jeopardize biodiversity. The combined effects of these threats will soon become detrimental to humans since provision of ecosystem services, such as protein from capture fisheries, can only be sustained if waters remain healthy. Climate change poses an insidious existential threat to freshwater biodiversity in the Anthropocene, but immediate risks from dams, habitat degradation and pollution could well be far greater.
In this Essay, Dudgeon describes the threats posed by climate change to freshwater biodiversity in the Anthropocene, as well as the more immediate risks from dams, habitat degradation and pollution, which could actually have a greater impact.
World Scientists’ Warning to Humanity RIPPLE, WILLIAM J.; WOLF, CHRISTOPHER; NEWSOME, THOMAS M. ...
Bioscience,
12/2017, Letnik:
67, Številka:
12
Journal Article
Coastal zones, the world’s most densely populated regions, are increasingly threatened by climate change stressors — rising and warming seas, intensifying storms and droughts, and acidifying oceans. ...Although coastal zones have been affected by local human activities for centuries, how local human impacts and climate change stressors may interact to jeopardize coastal ecosystems remains poorly understood. Here we provide a review on interactions between climate change and local human impacts (e.g., interactions between sea level rise and anthropogenic land subsidence, which are forcing Indonesia to relocate its capital city) in the coastal realm. We highlight how these interactions can impair and, at times, decimate a variety of coastal ecosystems, and examine how understanding and incorporating these interactions can reshape theory on climate change impacts and ecological resilience. We further discuss implications of interactions between climate change and local human impacts for coastal conservation and elucidate the context when and where local conservation is more likely to buffer the impacts of climate change, attempting to help reconcile the growing debate about whether to shift much of the investment in local conservation to global CO2 emission reductions. Our review underscores that an enhanced understanding of interactions between climate change and local human impacts is of profound importance to improving predictions of climate change impacts, devising climate-smart conservation actions, and helping enhance adaption of coastal societies to climate change in the Anthropocene.
He and Silliman explain how local human activity and global climate change interact to impact coastal ecosystems, arguing that conservation measures enacted at a local level can help buffer the effects of climate change.
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