Neutrophils Oppose Uterine Epithelial Carcinogenesis via Debridement of Hypoxic Tumor Cells.

Abstract:

: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.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Blaisdell A,Crequer A,Columbus D,Daikoku T,Mittal K,Dey SK,Erlebacher A

doi

10.1016/j.ccell.2015.11.005

subject

Has Abstract

pub_date

2015-12-14 00:00:00

pages

785-799

issue

6

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(15)00426-2

journal_volume

28

pub_type

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