The Measure of DAMPs and a role for S100A8 in recruiting suppressor cells in breast cancer lung metastasis

Abstract

To determine whether there was a relationship between damage associated molecular pattern molecule (DAMP) expression and recruitment of suppressor cells to sites of metastasis we measured relative expression of DAMPs, regulatory T cells (Tregs), and myeloid derived suppressor cells (MDSC) in mice at various stages of breast cancer progression using the 4T1 model. Although S100A8 was expressed at relatively low levels in the tumor cells, expression was 100-fold higher in the lung and liver which are common sites of metastasis for this tumor. Despite the relatively high level of S100A8 expression in the lungs of naïve mice, the level of expression increased further and was significantly elevated after only 7 days of tumor growth. The same pattern was observed for MDSC, and both S100A8 and MDSC expression peaked in the lungs of mice following 21 days of tumor growth. Characterization of MDSC from the lungs revealed expression of RAGE, and the cells were capable of migrating in a dose-dependent manner toward S100A8. In addition, the MDSC expressed low levels of MHC Class I, MHC Class II, CD80, and secreted TGF-β. Taken together, these data suggest that expression of S100A8 in the lungs may facilitate recruitment of MDSC, which may in turn aid in establishing a metastatic niche capable of suppressing a localized immune response.

• Breast cancer
• metastasis
• myeloid derived suppressor cells
• S100A8

Declaration of interest

This work was supported by the National Institutes of Health R15CA137858 to R.A.K., and by a grant from the Howard Hughes Medical Institute to Lafayette College under the Precollege and Undergraduate Science Education Program. The Department of Biology and Lafayette College Excel Scholar program also supported this work.

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.