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Extracellular signaling through the microenvironment: a hypothesis relating carcinogenesis, bystander effects, and genomic instabilityCell growth, differentiation and death are directed in large part by extracellular signaling through the interactions of cells with other cells and with the extracellular matrix; these interactions are in turn modulated by cytokines and growth factors, i.e. the microenvironment. Here we discuss the idea that extracellular signaling integrates multicellular damage responses that are important deterrents to the development of cancer through mechanisms that eliminate abnormal cells and inhibit neoplastic behavior. As an example, we discuss the action of transforming growth factor beta (TGFB1) as an extracellular sensor of damage. We propose that radiation-induced bystander effects and genomic instability are, respectively, positive and negative manifestations of this homeostatic process. Bystander effects exhibited predominantly after a low-dose or a nonhomogeneous radiation exposure are extracellular signaling pathways that modulate cellular repair and death programs. Persistent disruption of extracellular signaling after exposure to relatively high doses of ionizing radiation may lead to the accumulation of aberrant cells that are genomically unstable. Understanding radiation effects in terms of coordinated multicellular responses that affect decisions regarding the fate of a cell may necessitate re-evaluation of radiation dose and risk concepts and provide avenues for intervention.
Document ID
20040088720
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Barcellos-Hoff, M. H.
(Lawrence Berkeley National Laboratory, University of California Berkeley, California 94720, United States)
Brooks, A. L.
Chatterjee, A.
Date Acquired
August 21, 2013
Publication Date
November 1, 2001
Publication Information
Publication: Radiation research
Volume: 156
Issue: 5 Pt 2
ISSN: 0033-7587
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: R01-CA74053
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Radiation Health
Non-NASA Center

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