title: 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.
authors.affiliation: Department of Biology, Lafayette College , Easton, PA , USA.
authors.forename: Christine N
authors.initials: CN
authors.lastname: Vrakas
authors.forename: Ryan M
authors.initials: RM
authors.lastname: O'Sullivan
authors.forename: Samantha E
authors.initials: SE
authors.lastname: Evans
authors.forename: DaMarcus A
authors.initials: DA
authors.lastname: Ingram
authors.forename: Carli B
authors.initials: CB
authors.lastname: Jones
authors.forename: Tiffany
authors.initials: T
authors.lastname: Phuong
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kurt
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D039481:CD11b Antigen / Q000378:metabolism; D040501:Calgranulin A / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000556:secondary*; D051379:Mice; D022423:Myeloid Cells / Q000276:immunology / Q000378:metabolism*; D047368:Tumor Burden
chemical_list: D039481:CD11b Antigen; D040501:Calgranulin A
keywords: Breast cancer; S100A8; metastasis; myeloid derived suppressor cells