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

被引：185

作者：

Lisanti, Michael P. ^{[1
,2
,3
,4
,5
,6
]}

Martinez-Outschoorn, Ubaldo E. ^{[1
,2
,3
,4
]}

Lin, Zhao ^{[1
,2
,3
]}

Pavlides, Stephanos ^{[1
,2
,3
]}

Whitaker-Menezes, Diana ^{[1
,2
,3
]}

Pestell, Richard G. ^{[1
,2
,3
]}

Howell, Anthony ^{[5
,6
]}

Sotgia, Federica ^{[1
,5
,6
]}

机构：

[1] Thomas Jefferson Univ, Jefferson Stem Cell Biol & Regenerat Med Ctr, Philadelphia, PA 19107 USA

[2] Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Stem Cell Biol & Regenerat Med, Philadelphia, PA 19107 USA

[3] Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Canc Biol, Philadelphia, PA 19107 USA

[4] Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Med Oncol, Philadelphia, PA 19107 USA

[5] Univ Manchester, Manchester Breast Ctr, Manchester M13 9PL, Lancs, England

[6] Univ Manchester, Breakthrough Breast Canc Res Unit, Paterson Inst Canc Res, Sch Canc Enabling Sci & Technol,Manchester Acad H, Manchester M13 9PL, Lancs, England

来源：

CELL CYCLE | 2011年 / 10卷 / 15期

基金：

欧洲研究理事会;

关键词：

hydrogen peroxide; tumor stroma; microenvironment; aging; DNA damage; inflammation; NF kappa B; cancer metabolism; HIF1; autophagy; hypoxia; oxidative stress; seed and soil hypothesis; IDIOPATHIC PULMONARY-FIBROSIS; EXHALED BREATH CONDENSATE; KAPPA-B ACTIVATION; TUMOR STROMA MODEL; OXIDATIVE STRESS; ENERGY-METABOLISM; ALLOGRAFT-REJECTION; HEPATIC METASTASIS; ACATALASEMIC MICE; TARGETED DELIVERY;

D O I：

10.4161/cc.10.15.16870

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 (NF kappa B). 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.

引用

页码：2440 / 2449

页数：10

共 137 条

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