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    Hydrogen peroxide fuels aging, inflammation, cancer metabolism and metastasis: the seed and soil also needs "fertilizer".

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    Authors
    Lisanti, Michael P
    Martinez-Outschoorn, U E
    Lin, Z
    Pavlides, S
    Whitaker-Menezes, D
    Pestell, R G
    Howell, Anthony
    Sotgia, F
    Affiliation
    The Jefferson Stem Cell Biology and Regenerative Medicine Center, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
    Issue Date
    2011-08-01
    
    Metadata
    Show full item record
    Abstract
    In 1889, Dr. Stephen Paget proposed the "seed and soil" hypothesis, which states that cancer cells (the seeds) need the proper microenvironment (the soil) for them to grow, spread and metastasize systemically. In this hypothesis, Dr. Paget rightfully recognized that the tumor microenvironment has an important role to play in cancer progression and metastasis. In this regard, a series of recent studies have elegantly shown that the production of hydrogen peroxide, by both cancer cells and cancer-associated fibroblasts, may provide the necessary "fertilizer," by driving accelerated aging, DNA damage, inflammation and cancer metabolism, in the tumor microenvironment. By secreting hydrogen peroxide, cancer cells and fibroblasts are mimicking the behavior of immune cells (macrophages/neutrophils), driving local and systemic inflammation, via the innate immune response (NFκB). Thus, we should consider using various therapeutic strategies (such as catalase and/or other anti-oxidants) to neutralize the production of cancer-associated hydrogen peroxide, thereby preventing tumor-stroma co-evolution and metastasis. The implications of these findings for overcoming chemo-resistance in cancer cells are also discussed in the context of hydrogen peroxide production and cancer metabolism.
    Citation
    Hydrogen peroxide fuels aging, inflammation, cancer metabolism and metastasis: the seed and soil also needs "fertilizer". 2011, 10 (15):2440-9 Cell Cycle
    Journal
    Cell Cycle
    URI
    http://hdl.handle.net/10541/230936
    DOI
    10.4161/cc.10.15.16870
    PubMed ID
    21734470
    Type
    Article
    Language
    en
    ISSN
    1551-4005
    ae974a485f413a2113503eed53cd6c53
    10.4161/cc.10.15.16870
    Scopus Count
    Collections
    All Christie Publications
    Medical Oncology

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