| Cell death in the neighbourhood: direct microenvironmental effects of apoptosis in normal and neoplastic tissues. | |
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MedLine Citation:
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PMID: 20976688 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Here we consider the impact of the physiological cell-death programme on normal tissue homeostasis and on disease pathogenesis, with particular reference to evolution and progression of neoplasia. We seek to describe the direct contributions played by apoptosis in creating the microenvironments of normal and malignant tissues and to discuss the molecular mechanisms underlying the elements of the '3Rs' that define the meaning of apoptosis: recognition, response, and removal. Apoptotic cells elicit responses in other cell types-both phagocytic and non-phagocytic-through short- and long-range signalling modes that range from direct contact to intercellular communication via membrane-bound microparticles. Such cellular responses include migration, proliferation, and differentiation, as well as production of immunomodulatory and anti-inflammatory mediators together with, in the case of phagocytes, engulfment, and breakdown of apoptotic cells. In normal tissues, the removal of apoptotic cells is rapid and typically non-phlogistic. We discuss the importance of this clearance process in tissue homeostasis and the consequences of its failure in disease pathogenesis. Using the typical cell culture environment in vitro as an illustrative example in which apoptosis occurs commonly in the absence of the removal mechanisms, we also discuss the inhibitory effects of persistent apoptotic cells on their otherwise viable neighbours. Since apoptosis is a common and sustained event in high-grade malignancies, we hypothesize on its purposeful role in conditioning the tumour microenvironment. We propose that apoptosis subserves several pro-tumour functions-trophic, anti-inflammatory, and immunomodulatory-and we identify strategies targeting host responses to apoptotic cells as promising modes of future therapies that could be applied to multiple cancer types in which tumour-cell apoptosis is active. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
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Authors:
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Christopher D Gregory; John D Pound |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2010-9-27 |
Journal Detail:
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Title: The Journal of pathology Volume: - ISSN: 1096-9896 ISO Abbreviation: - Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-10-26 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0204634 Medline TA: J Pathol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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MRC Centre for Inflammation Research, University of Edinburgh, Queens Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK and ImmunoSolv Limited, The Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB, UK. |
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