肿瘤微环境
癌细胞
癌症
转移
炎症
生物
癌症研究
过氧化氢
背景(考古学)
免疫系统
先天免疫系统
免疫学
生物化学
古生物学
遗传学
作者
Michael P. Lisanti,Ubaldo Martinez‐Outschoorn,Lin Zhao,Stephanos Pavlides,Diana Whitaker‐Menezes,Richard G. Pestell,Anthony Howell,Federica Sotgia
出处
期刊:Cell Cycle
[Informa]
日期:2011-08-01
卷期号:10 (15): 2440-2449
被引量:202
标识
DOI:10.4161/cc.10.15.16870
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 (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.
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