S100A7 Enhances Mammary Tumorigenesis through Upregulation of Inflammatory Pathways

Abstract

S100A7/Psoriasin, a member of the epidermal differentiation complex, is widely overexpressed in invasive ER-negative (ERα-) 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 homolog mS100a7a15, enhanced cell proliferation and upregulated various pro-inflammatory molecules in ERα- 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 to 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 pro-metastatic gene expression and recruitment of tumor-associated macrophages (TAMs). Notably, in vivo depletion of TAM inhibited the effects of mS100a7a15 induction on tumor growth and angiogenesis. Further, introduction of soluble hS100A7 or mS100a7a15 enhanced chemotaxis of macrophages via activation of RAGE receptors. In summary, our work employed a powerful new model system to demonstrate that S100A7 enhances breast tumor growth and metastasis by activating proinflammatory and metastatic pathways.

Retrospective Proteomic Screening of 100 Breast Cancer Tissues

“…Its pssible role in breast cancer has been discussed in a previous work by our group [170] and other authors [171][172][173]. S10A8 (S100A8), S10A9 (S100A9).…”

HMGB1, S100 proteins and other RAGE ligands in cancer - markers, mediators and putative therapeutic targets

“…In pancreatic cancer, the expression of S100A4 and S100P was associated with drug resistence, differentiation, metastasis and clinical outcome and S100A11 and S100P, and possibly also S100A2 and S100A6 were related to the unfavorable outcome of the patients after surgical resection 61 . S100A7/psoriasin was highly expressed in high-grade ductal breast carcinoma in situ 62 , high-grade comedo ductal carcinoma in situ with higher risk of local recurrence 63 and in invasive estrogen receptor negative breast cancer 64 . Its expression was related to ductal hyperplasia, recruitment of tumor-associated macrophages, tumor growth, angiogenesis and metastasis.…”

New Insights into the Occurrence of Matrix Metalloproteases -2 and -9 in a Cohort of Breast Cancer Patients and Proteomic Correlations

“…S100 proteins. The group of S100-A7,-A8 and -A9, calcium binding proteins are known to exert several functions in normal and tumoral tissues, where they may be expressed at high levels as has been reported by our group [49] and other authors [50][51][52][53]. Their correlation with MMP9 has never been proposed before.…”