IL-6 secreted from senescent mesenchymal stem cells promotes proliferation and migration of breast cancer cells

• Published in: PloS one Vol. 9; no. 11; p. e113572
• Main Authors: Di, Guo-Hu, Liu, Yang, Lu, Ying, Liu, Jin, Wu, Chutse, Duan, Hai-Feng
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.11.2014; Public Library of Science (PLoS)
• Subjects: Aging; Analysis; Animals; Biology and Life Sciences; Blotting, Western; Bone marrow; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Breast Neoplasms - therapy; Cancer; Cancer cells; Cancer therapies; Cell cycle; Cell division; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Cells, Cultured; Cellular Senescence - drug effects; Conditioning; Culture Media, Conditioned - metabolism; Culture Media, Conditioned - pharmacology; Development and progression; Endothelin-1 - metabolism; Female; Fetal Blood - cytology; Genetic transformation; Genotoxicity; Health aspects; Humans; Hydrogen Peroxide - pharmacology; Interleukin 6; Interleukin-6 - pharmacology; Interleukin-6 - secretion; Laboratories; MCF-7 Cells; Medicine; Medicine and Health Sciences; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Mesenchyme; Mice; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Oxidants - pharmacology; Oxidative stress; Phosphorylation; Phosphorylation - drug effects; Senescence; Skin & tissue grafts; Somatic cells; Stat3 protein; STAT3 Transcription Factor - metabolism; Stem cell transplantation; Stem cells; Therapeutic applications; Transformation; Tumor cells; Tumors; Umbilical cord; Xenograft Model Antitumor Assays; Xenografts; Beijing China; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0113572

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.