The paradox of tumor-associated neutrophils: fueling tumor growth with cytotoxic substances.
Human cancers are comprised of numerous cell types including neutrophils. Although often ignored, neutrophils are frequently present at sites of tumorigenesis including the kidney, breast, colon and lung. These cells possess substances such as reactive oxygen species and proteinases that are capable of modifying tumor growth and invasiveness. This review addresses recent reports describing both pro-host and pro-tumor roles for neutrophils and neutrophil-derived substances and will examine the alterations in neutrophil behavior that explain this apparent biological discrepancy. Unfortunately, with the exception of investigator driven manipulation of neutrophil function, these cells function overwhelmingly against the host in the setting of cancer. Many cancers are capable of recruiting neutrophils to sites of tumorigenesis where they enhance tumor growth. Identification of the neutrophil-derived substances that promote tumor growth may yield novel therapeutic approaches to inhibit cancer progression. Alternatively, strategies designed to generate highly activated and cytotoxic neutrophils within the tumor microenvironment may provide a means to unleash the tumoricidal potential of the host's innate immune response.
Houghton
A McGarry
AM
Division of Pulmonary, Allergy & Critical Care Medicine, Department of Medicine, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. houghtonm@dom.pitt.edu
D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D016207:Cytokines; D017382:Reactive Oxygen Species; D010447:Peptide Hydrolases; D019272:Leukocyte Elastase; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9