title: Human bone marrow-derived MSCs can home to orthotopic breast cancer tumors and promote bone metastasis.
abstract: American women have a nearly 25% lifetime risk of developing breast cancer, with 20% to 40% of these patients developing life-threatening metastases. More than 70% of patients presenting with metastases have skeletal involvement, which signals progression to an incurable stage. Tumor-stroma cell interactions are only superficially understood, specifically regarding the ability of stromal cells to affect metastasis. In vivo models show that exogenously supplied human bone marrow-derived stem cells (hBMSC) migrate to breast cancer tumors, but no reports have shown endogenous hBMSC migration from the bone to primary tumors. Here, we present a model of in vivo hBMSC migration from a physiologic human bone environment to human breast tumors. Furthermore, hBMSCs alter tumor growth and bone metastasis frequency. These may home to certain breast tumors based on tumor-derived TGF-β1. Moreover, at the primary tumor level, interleukin 17B (IL-17B)/IL-17BR signaling may mediate interactions between hBMSCs and breast cancer cells.
authors.affiliation: Program in Genetics, Sackler School of Biomedical Sciences, Tufts University, Boston, Massachusetts, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Goldstein
authors.forename: Michaela R
authors.initials: MR
authors.lastname: Reagan
authors.forename: Kristen
authors.initials: K
authors.lastname: Anderson
authors.forename: David L
authors.initials: DL
authors.lastname: Kaplan
authors.forename: Michael
authors.initials: M
authors.lastname: Rosenblatt
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D001859:Bone Neoplasms / Q000556:secondary*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000473:pathology* / Q000556:secondary; D002450:Cell Communication / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D053722:Receptors, Interleukin-17 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D014183:Transplantation, Heterologous
chemical_list: D020381:Interleukin-17; D053722:Receptors, Interleukin-17; D016212:Transforming Growth Factor beta