Role of S100A7 in regulating inflammatory pathways during mammary tumorigenesis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Deol Yadwinder
PROVIDER: S-ECPF-GEOD-32052 | biostudies-other |
REPOSITORIES: biostudies-other
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2011-10-26 | E-GEOD-32052 | biostudies-arrayexpress
Project description:Psoriasin (S100A7) has been shown to be highly expressed in invasive estrogen receptor negative breast cancers. Expression of S100A7 in human breast tumors represents a poor prognostic marker and correlates with lymphocyte infiltration in high-grade morphology. Recent studies have shown that S100A7 downregulation in ERα- cells lines inhibits tumor growth in in vivo mouse model systems. However, not much is known about its mechanisms in regulating breast cancers. We used microarrays to determine the global differential gene expression in S100A7 overexpressing breast cells and vector control cells and found out that most of the genes involved in inflammatory pathways were differentially regulated.
2011-10-27 | GSE32052 | GEO
Project description: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.
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