IL17 Promotes Mammary Tumor Progression by Changing the Behavior of Tumor Cells and Eliciting Tumorigenic Neutrophils Recruitment

Autor(es)

Benevides, Luciana ^[1] ; da Fonseca, Denise Morais ^[1] ; Donate, Paula Barbim ^[1] ; Tiezzi, Daniel Guimaraes ^[2] ; De Carvalho, Daniel D. ^{[3, 4]} ; de Andrade, Jurandyr M. ^[2] ; Martins, Gislaine A. ^{[5, 6]} ; Silva, Joao S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, BR-14049900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Gynecol & Obstet, Breast Dis Div, BR-14049900 Sao Paulo - Brazil

^[3] Univ Toronto, Dept Med Biophys, Toronto, ON - Canada

^[4] Univ Toronto, Ontario Canc Inst, Princess Margaret Canc Ctr, Univ Hlth Network, Toronto, ON M5S 1A1 - Canada

^[5] Cedars Sinai Med Ctr, F Widjaja Fdn Inflammatory Bowel & Immunobiol Res, Los Angeles, CA 90048 - USA

^[6] Cedars Sinai Med Ctr, Dept Med & Biomed Sci, Los Angeles, CA 90048 - USA

• Tipo de documento: Artigo Científico
• Fonte: Cancer Research; v. 75, n. 18, p. 3788-3799, SEP 15 2015.
• Citações Web of Science: 50

Resumo

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 TNF alpha, 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. (C) 2015 AACR. (AU)

• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 12/08240-8 - Papel de Blimp-1 na diferenciação e função das células Th9
• Beneficiário: Luciana Benevides
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 12/14524-9 - Modulação da diferenciação de linfócitos T em infecções por protozoários, fungos e bactérias
• Beneficiário: João Santana da Silva
• Modalidade de apoio: Auxílio à Pesquisa - Temático