title: IL17 Promotes Mammary Tumor Progression by Changing the Behavior of Tumor Cells and Eliciting Tumorigenic Neutrophils Recruitment.
abstract: The aggressiveness of invasive ductal carcinoma (IDC) of the breast is associated with increased IL17 levels. Studying the role of IL17 in invasive breast tumor pathogenesis, we found that metastatic primary tumor-infiltrating T lymphocytes produced elevated levels of IL17, whereas IL17 neutralization inhibited tumor growth and prevented the migration of neutrophils and tumor cells to secondary disease sites. Tumorigenic neutrophils promote disease progression, producing CXCL1, MMP9, VEGF, and TNFα, and their depletion suppressed tumor growth. IL17A also induced IL6 and CCL20 production in metastatic tumor cells, favoring the recruitment and differentiation of Th17. In addition, IL17A changed the gene-expression profile and the behavior of nonmetastatic tumor cells, causing tumor growth in vivo, confirming the protumor role of IL17. Furthermore, high IL17 expression was associated with lower disease-free survival and worse prognosis in IDC patients. Thus, IL17 blockade represents an attractive approach for the control of invasive breast tumors.
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Benevides
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Denise Morais
authors.initials: DM
authors.lastname: da Fonseca
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Paula Barbim
authors.initials: PB
authors.lastname: Donate
authors.affiliation: Department of Gynecology and Obstetrics, Breast Disease Division, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Daniel Guimarães
authors.initials: DG
authors.lastname: Tiezzi
authors.affiliation: Ontario Cancer Institute, Princess Margaret Cancer Centre, University Health Network, and Department of Medical Biophysics, University of Toronto, Toronto, Canada.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: De Carvalho
authors.affiliation: Department of Gynecology and Obstetrics, Breast Disease Division, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Jurandyr M
authors.initials: JM
authors.lastname: de Andrade
authors.affiliation: F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute and Department of Medicine and Biomedical Science, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: Gislaine A
authors.initials: GA
authors.lastname: Martins
authors.affiliation: Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil. jsdsilva@fmrp.usp.br.
authors.forename: João S
authors.initials: JS
authors.lastname: Silva
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000737:chemistry / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000276:immunology / Q000401:mortality / Q000556:secondary*; D002634:Chemotaxis, Leukocyte / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020381:Interleukin-17 / Q000032:analysis / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D011379:Prognosis; D058504:Th17 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; C508717:IL17A protein, human; C098680:Il17a protein, mouse; D020381:Interleukin-17; D009363:Neoplasm Proteins