S100A7 enhances mammary tumorigenesis through upregulation of inflammatory pathways

Mohd W. Nasser, Zahida Qamri, Yadwinder S. Deol, Janani Ravi, Catherine A. Powell, Prashant Trikha, Reto A. Schwendener, Xue Feng Bai, Konstantin Shilo, Xianghong Zou, Gustavo Leone, Ronald Wolf, Stuart H. Yuspa, Ramesh K. Ganju

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

S100A7/psoriasin, a member of the epidermal differentiation complex, is widely overexpressed in invasive estrogen receptor (ER)a-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 ERa-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 ofTAMinhibited 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.

Original languageEnglish (US)
Pages (from-to)604-615
Number of pages12
JournalCancer Research
Volume72
Issue number3
DOIs
StatePublished - Feb 1 2012

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'S100A7 enhances mammary tumorigenesis through upregulation of inflammatory pathways'. Together they form a unique fingerprint.

Cite this