Neutrophils Oppose Uterine Epithelial Carcinogenesis via Debridement of Hypoxic Tumor Cells.
Neutrophils Oppose Uterine Epithelial Carcinogenesis via Debridement of Hypoxic Tumor Cells.
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DOI：
10.1016/j.ccell.2015.11.005
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发表时间：
2015-12-14
期刊：
影响因子：
50.3
通讯作者：
Erlebacher A
中科院分区：
文献类型：
--
作者：
Blaisdell A;Crequer A;Columbus D;Daikoku T;Mittal K;Dey SK;Erlebacher A
尽管使用了大量的细胞毒性药物，但多形性中性粒细胞（PMNs）在很大程度上被认为是促进癌症发展的因素。使用小鼠模型的PTEN缺陷的子宫癌，我们描述了一个令人惊讶的抑制作用，中性粒细胞在上皮癌的发生。通过诱导肿瘤细胞脱离基底膜，中性粒细胞阻碍早期肿瘤生长并延缓恶性进展。出乎意料的是，PMN募集和肿瘤生长控制独立于淋巴细胞和细胞衰老发生，而是作为肿瘤对缺氧的内在炎症反应的一部分。在人类中，PMN基因特征与几种癌症亚型的生存率提高相关，包括PTEN缺陷型子宫癌。这些研究结果提供了深入了解肿瘤相关的中性粒细胞，并揭示了一个上下文特定的能力，中性粒细胞直接打击肿瘤发生。
Polymorphonuclear neutrophils (PMNs) are largely considered to foster cancer development despite wielding an arsenal of cytotoxic agents. Using a mouse model of PTEN-deficient uterine cancer, we describe a surprising inhibitory role for PMNs in epithelial carcinogenesis. By inducing tumor cell detachment from the basement membrane, PMNs impeded early-stage tumor growth and retarded malignant progression. Unexpectedly, PMN recruitment and tumor growth control occurred independently of lymphocytes and cellular senescence and instead ensued as part of the tumor's intrinsic inflammatory response to hypoxia. In humans, a PMN gene signature correlated with improved survival in several cancer subtypes, including PTEN-deficient uterine cancer. These findings provide insight into tumor-associated PMNs and reveal a context-specific capacity for PMNs to directly combat tumorigenesis.