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IL-6 Secreted from Senescent Mesenchymal Stem Cells Promotes Proliferation and Migration of Breast Cancer Cells
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IL-6 Secreted from Senescent Mesenchymal Stem Cells Promotes Proliferation and Migration of Breast Cancer Cells
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Journal Article
IL-6 Secreted from Senescent Mesenchymal Stem Cells Promotes Proliferation and Migration of Breast Cancer Cells
2014
Overview
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.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Analysis
/ Animals
/ Breast Neoplasms - metabolism
/ Breast Neoplasms - pathology
/ Cancer
/ Cell Movement - drug effects
/ Cell Proliferation - drug effects
/ Cellular Senescence - drug effects
/ Culture Media, Conditioned - metabolism
/ Culture Media, Conditioned - pharmacology
/ Female
/ Humans
/ Hydrogen Peroxide - pharmacology
/ Interleukin-6 - pharmacology
/ Medicine
/ Medicine and Health Sciences
/ Mesenchymal Stem Cell Transplantation - methods
/ Mesenchymal Stromal Cells - cytology
/ Mesenchymal Stromal Cells - metabolism
/ Mice
/ Neovascularization, Pathologic - metabolism
/ Neovascularization, Pathologic - pathology
/ Phosphorylation - drug effects
/ STAT3 Transcription Factor - metabolism
/ Tumors
