title: 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.
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, NY 10016, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Blaisdell
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, NY 10016, USA.
authors.forename: Amandine
authors.initials: A
authors.lastname: Crequer
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, NY 10016, USA.
authors.forename: Devin
authors.initials: D
authors.lastname: Columbus
authors.affiliation: Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Takiko
authors.initials: T
authors.lastname: Daikoku
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, NY 10016, USA.
authors.forename: Khush
authors.initials: K
authors.lastname: Mittal
authors.affiliation: Division of Reproductive Sciences, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Sudhansu K
authors.initials: SK
authors.lastname: Dey
authors.affiliation: Department of Pathology, NYU School of Medicine, New York, NY 10016, USA; NYU Cancer Institute, NYU Langone Medical Center, New York, NY 10016, USA. Electronic address: adrian.erlebacher@nyumc.org.
authors.forename: Adrian
authors.initials: A
authors.lastname: Erlebacher
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D018269:Carcinoma, Endometrioid / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D002448:Cell Adhesion; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002633:Chemotaxis; D019295:Computational Biology; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling; D018014:Gene Transfer Techniques; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics; D009367:Neoplasm Staging; D018375:Neutrophil Activation; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D010052:Ovariectomy; D051059:PTEN Phosphohydrolase / Q000172:deficiency / Q000235:genetics; D010587:Phagocytosis; D016184:Receptors, Colony-Stimulating Factor / Q000172:deficiency / Q000235:genetics; D023063:Receptors, Interleukin-8B / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D013997:Time Factors; D047368:Tumor Burden; D059016:Tumor Microenvironment; D014599:Uterus / Q000201:enzymology / Q000276:immunology* / Q000473:pathology
chemical_list: D018836:Inflammation Mediators; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016184:Receptors, Colony-Stimulating Factor; D023063:Receptors, Interleukin-8B; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse