title: Hydrogen peroxide fuels aging, inflammation, cancer metabolism and metastasis: the seed and soil also needs "fertilizer".
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.
authors: The Jefferson Stem Cell Biology and Regenerative Medicine Center, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA. michael.lisanti@kimmelcancercenter.org
authors: Michael P
authors: MP
authors: Lisanti
authors: Ubaldo E
authors: UE
authors: Martinez-Outschoorn
authors: Zhao
authors: Z
authors: Lin
authors: Stephanos
authors: S
authors: Pavlides
authors: Diana
authors: D
authors: Whitaker-Menezes
authors: Richard G
authors: RG
authors: Pestell
authors: Anthony
authors: A
authors: Howell
authors: Federica
authors: F
authors: Sotgia
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D016922:Cellular Senescence; D004249:DNA Damage; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009362:Neoplasm Metastasis; D018384:Oxidative Stress; D059016:Tumor Microenvironment
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007773:Lactates; D016328:NF-kappa B; D006861:Hydrogen Peroxide