Faculty Collaboration Database

S100A7 enhances mammary tumorigenesis through upregulation of inflammatory pathways. Cancer Res 2012 Feb 01;72(3):604-15

Date

12/14/2011

Pubmed ID

22158945

Pubmed Central ID

PMC3271140

DOI

10.1158/0008-5472.CAN-11-0669

Scopus ID

2-s2.0-84856527732 (requires institutional sign-in at Scopus site)   97 Citations

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.

Author List

Nasser MW, Qamri Z, Deol YS, Ravi J, Powell CA, Trikha P, Schwendener RA, Bai XF, Shilo K, Zou X, Leone G, Wolf R, Yuspa SH, Ganju RK

Author

Gustavo Leone PhD Sr Associate Dean, Director, Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Blotting, Western
Breast Neoplasms
Cell Line, Tumor
Cell Proliferation
Chemokines
Chemotaxis
Cytokines
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Inflammation
Macrophages
Male
Mammary Neoplasms, Experimental
Mice
Mice, Transgenic
Neoplasm Metastasis
Oligonucleotide Array Sequence Analysis
Receptor for Advanced Glycation End Products
Receptors, Immunologic
Reverse Transcriptase Polymerase Chain Reaction
S100 Calcium Binding Protein A7
S100 Proteins
Signal Transduction
Up-Regulation
Vascular Endothelial Growth Factor A