title: IL-6 secreted from senescent mesenchymal stem cells promotes proliferation and migration of breast cancer cells.
abstract: Human mesenchymal stem cells (hMSCs) are currently investigated for a variety of therapeutic applications. However, MSCs isolated from primary tissue cannot meet clinical grade needs and should be expanded in vitro for several passages. Although hMSCs show low possibility for undergoing oncogenic transformation, they do, similar to other somatic cells, undergo cellular senescence and their therapeutic potential is diminished when cultured in vitro. However, the role of senescent MSCs in tumor progression remains largely elusive. In the current study, by establishing senescent human umbilical cord mesenchymal stem cells (s-UCMSCs) through the replicative senescence model and genotoxic stress induced premature senescence model, we show that s-UCMSCs significantly stimulate proliferation and migration of breast cancer cells in vitro and tumor progression in a co-transplant xenograft mouse model compared with 'young' counterparts (defined as MSCs at passage 5, in contrast to senescent MSCs at passage 45). In addition, we identified IL-6, a known pleiotropic cytokine, as a principal mediator for the tumor-promoting activity of s-UCMSCs by induction of STAT3 phosphorylation. Depletion of IL-6 from s-UCMSCs conditioned medium partially abrogated the stimulatory effect of s-UCMSCs on the proliferation and migration of breast tumor cells.
authors.affiliation: Beijing Institute of Radiation Medicine (BIRM), No. 27, Taiping Road, Haidian District, Beijing 100850, China; State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, 5 Yan'erdao Road, Qingdao 266071, China.
authors.forename: Guo-Hu
authors.initials: GH
authors.lastname: Di
authors.affiliation: Beijing Institute of Radiation Medicine (BIRM), No. 27, Taiping Road, Haidian District, Beijing 100850, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The 307 Hospital, No. 8, Dongdajie Street, Fengtai District, Beijing 100071, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Beijing Institute of Radiation Medicine (BIRM), No. 27, Taiping Road, Haidian District, Beijing 100850, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Beijing Institute of Radiation Medicine (BIRM), No. 27, Taiping Road, Haidian District, Beijing 100850, China.
authors.forename: Chutse
authors.initials: C
authors.lastname: Wu
authors.affiliation: Beijing Institute of Radiation Medicine (BIRM), No. 27, Taiping Road, Haidian District, Beijing 100850, China.
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Duan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000378:metabolism / Q000494:pharmacology; D019332:Endothelin-1 / Q000378:metabolism; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology*; D061986:MCF-7 Cells; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology; D016877:Oxidants / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D017077:Culture Media, Conditioned; D019332:Endothelin-1; D015850:Interleukin-6; D016877:Oxidants; D050796:STAT3 Transcription Factor; D006861:Hydrogen Peroxide