RRC ID 45097
Author Kanehira M, Kikuchi T, Santoso A, Tode N, Hirano T, Ohkouchi S, Tamada T, Sugiura H, Harigae H, Ichinose M.
Title Human marrow stromal cells downsize the stem cell fraction of lung cancers by fibroblast growth factor 10.
Journal Mol Cell Biol
Abstract The functional interplay between cancer cells and marrow stromal cells (MSCs) has attracted a great deal of interest due to the MSC tropism for tumors but remains to be fully elucidated. In this study, we investigated human MSC-secreted paracrine factors that appear to have critical functions in cancer stem cell subpopulations. We show that MSC-conditioned medium reduced the cancer stem cell-enriched subpopulation, which was detected as a side population and quiescent (G0) cell cycle fraction in human lung cancer cells by virtue of fibroblast growth factor 10 (FGF10). This reduction of the stem cell-enriched fraction was also observed in lung cancer cells supplemented with recombinant human FGF10 protein. Moreover, supplementary FGF10 attenuated the expression of stemness genes encoding transcription factors, such as OCT3/4 and SOX2, and crippled the self-renewal capacity of lung cancer cells, as evidenced by the impaired formation of floating spheres in the suspension culture. We finally confirmed the therapeutic potential of the FGF10 treatment, which rendered lung cancer cells prone to a chemotherapeutic agent, probably due to the reduced cancer stem cell subpopulation. Collectively, these results add further clarification to the molecular mechanisms underlying MSC-mediated cancer cell kinetics, facilitating the development of future therapies.
Volume 34(15)
Pages 2848-56
Published 2014-8
DOI 10.1128/MCB.00871-13
PII MCB.00871-13
PMID 24865969
PMC PMC4135576
MeSH Animals Bone Marrow / metabolism Bone Marrow / pathology* Cell Line, Tumor Fibroblast Growth Factor 10 / metabolism* HeLa Cells Humans Lung Neoplasms / metabolism* Lung Neoplasms / pathology* MCF-7 Cells Mice Mice, Inbred BALB C Neoplastic Stem Cells / metabolism Neoplastic Stem Cells / pathology Stem Cells / metabolism Stem Cells / pathology* Stromal Cells / metabolism Stromal Cells / pathology* Transcription Factors / metabolism
IF 3.735
Times Cited 6
Human and Animal Cells