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

Michael P. Lisanti, Ubaldo E. Martinez-Outschoorn, Zhao Lin, Stephanos Pavlides, Diana Whitaker-Menezes, Richard G. Pestell, Anthony Howell, Federica Sotgia

    Research output: Contribution to journalArticlepeer-review

    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. © 2011 Landes Bioscience.
    Original languageEnglish
    Pages (from-to)2440-2449
    Number of pages9
    JournalCell Cycle
    Volume10
    Issue number15
    DOIs
    Publication statusPublished - 1 Aug 2011

    Keywords

    • Aging
    • Autophagy
    • Cancer metabolism
    • DNA damage
    • HIF1
    • Hydrogen peroxide
    • Hypoxia
    • Inflammation
    • Microenvironment
    • NFκB
    • Oxidative stress
    • Seed and soil hypothesis
    • Tumor stroma

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