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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-58661

Nasser, M W; Qamri, Z; Deol, Y S; Ravi, J; Powell, C A; Trikha, P; Schwendener, R A; Bai, X F; Shilo, K; Zou, X; Leone, G; Wolf, R; Yuspa, S H; Ganju, R K (2012). S100A7 Enhances Mammary Tumorigenesis through Upregulation of Inflammatory Pathways. Cancer Research, 72(3):604-615.

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Abstract

S100A7/psoriasin, a member of the epidermal differentiation complex, is widely overexpressed in invasive estrogen receptor (ER)α-negative breast cancers. However, it has not been established whether S100A7 contributes to breast cancer growth or metastasis. Here, we report the consequences of its expression on inflammatory pathways that impact breast cancer growth. Overexpression of human S100A7 or its murine homologue mS100a7a15 enhanced cell proliferation and upregulated various proinflammatory molecules in ERα-negative breast cancer cells. To examine in vivo effects, we generated mice with an inducible form of mS100a7a15 (MMTV-mS100a7a15 mice). Orthotopic implantation of MVT-1 breast tumor cells into the mammary glands of these mice enhanced tumor growth and metastasis. Compared with uninduced transgenic control mice, the mammary glands of mice where mS100a7a15 was induced exhibited increased ductal hyperplasia and expression of molecules involved in proliferation, signaling, tissue remodeling, and macrophage recruitment. Furthermore, tumors and lung tissues obtained from these mice showed further increases in prometastatic gene expression and recruitment of tumor-associated macrophages (TAM). Notably, in vivo depletion of TAM inhibited the effects of mS100a7a15 induction on tumor growth and angiogenesis. Furthermore, introduction of soluble hS100A7 or mS100a7a15 enhanced chemotaxis of macrophages via activation of RAGE receptors. In summary, our work used a powerful new model system to show that S100A7 enhances breast tumor growth and metastasis by activating proinflammatory and metastatic pathways. Cancer Res; 72(3); 604-15. ©2011 AACR.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research
DDC:570 Life sciences; biology
Language:English
Date:2012
Deposited On:02 Apr 2012 11:59
Last Modified:17 Jul 2014 18:56
Publisher:American Association for Cancer Research
ISSN:0008-5472
Publisher DOI:10.1158/0008-5472.CAN-11-0669
PubMed ID:22158945
Citations:Web of Science®. Times Cited: 20
Google Scholar™
Scopus®. Citation Count: 22

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