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: Luciana Benevides, Denise Morais da Fonseca, Paula Barbim Donate, Daniel Guimarães Tiezzi, Daniel D De Carvalho, Jurandyr M de Andrade, Gislaine A Martins, João S Silva
• Journal: Cancer research (Cancer Res) Vol. 75 Issue 18 Pg. 3788-99 (Sep 15 2015) ISSN: 1538-7445 [Electronic] United States
• PMID: 26208902 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2015 American Association for Cancer Research.

Chemical References

• Cytokines
• IL17A protein, human
• Il17a protein, mouse
• Interleukin-17
• Neoplasm Proteins

Topics

• Animals
• Breast Neoplasms (chemistry, immunology, mortality, pathology)
• Carcinoma, Ductal, Breast (chemistry, immunology, mortality, secondary)
• Chemotaxis, Leukocyte (physiology)
• Cytokines (biosynthesis, genetics, metabolism)
• Disease Progression
• Disease-Free Survival
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Interleukin-17 (analysis, antagonists & inhibitors, immunology, physiology)
• Lymphocytes, Tumor-Infiltrating (immunology, metabolism)
• Mammary Neoplasms, Experimental (immunology, pathology)
• Mice
• Mice, Inbred BALB C
• Neoplasm Proteins (analysis, antagonists & inhibitors, immunology, physiology)
• Neutrophils (immunology, metabolism)
• Prognosis
• Th17 Cells (immunology)