title: Breast cancer cells stimulate neutrophils to produce oncostatin M: potential implications for tumor progression.
abstract: Tumor-associated and tumor-infiltrating neutrophils (TAN) and macrophages (TAM) can account for as much as 50% of the total tumor mass in invasive breast carcinomas. It is thought that tumors secrete factors that elicit a wound-repair response from TAMs and TANs and that this response inadvertently stimulates tumor progression. Oncostatin M is a pleiotropic cytokine belonging to the interleukin-6 family that is expressed by several cell types including activated human T lymphocytes, macrophages, and neutrophils. Whereas oncostatin M can inhibit the proliferation of breast cancer cells in vitro, recent studies suggest that oncostatin M may promote tumor progression by enhancing angiogenesis and metastasis. In addition, neutrophils can be stimulated to synthesize and rapidly release large quantities of oncostatin M. In this article, we show that human neutrophils secrete oncostatin M when cocultured with MDA-MB-231 and T47D human breast cancer cells. Neutrophils isolated from whole blood or breast cancer cells alone express little oncostatin M by immunocytochemistry and ELISA, but neutrophils express and release high levels of oncostatin M when they are cocultured with breast cancer cells. In addition, we show that granulocyte-macrophage colony-stimulating factor produced by breast cancer cells and cell-cell contact are both necessary for the release of oncostatin M from neutrophils. Importantly, neutrophil-derived oncostatin M induces vascular endothelial growth factor from breast cancer cells in coculture and increases breast cancer cell detachment and invasive capacity, suggesting that neutrophils and oncostatin M may promote tumor progression in vivo.
authors.affiliation: Department of Biology, Boise State University, Boise, Idaho 83725, USA.
authors.forename: Marisa M
authors.initials: MM
authors.lastname: Queen
authors.forename: Randall E
authors.initials: RE
authors.lastname: Ryan
authors.forename: Ryan G
authors.initials: RG
authors.lastname: Holzer
authors.forename: Cynthia R
authors.initials: CR
authors.lastname: Keller-Peck
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Jorcyk
mesh_terms: D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D017077:Culture Media, Conditioned; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology; D006801:Humans; D009361:Neoplasm Invasiveness; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism*; D053683:Oncostatin M; D010455:Peptides / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D000906:Antibodies; D017077:Culture Media, Conditioned; C508351:OSM protein, human; D010455:Peptides; D042461:Vascular Endothelial Growth Factor A; D053683:Oncostatin M; D016178:Granulocyte-Macrophage Colony-Stimulating Factor