title: Human marrow stromal cells downsize the stem cell fraction of lung cancers by fibroblast growth factor 10.
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.
authors.affiliation: Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kanehira
authors.affiliation: Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan Department of Respiratory Medicine, Tohoku University Hospital, Sendai, Japan kikuchi@rm.med.tohoku.ac.jp.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kikuchi
authors.affiliation: Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Arif
authors.initials: A
authors.lastname: Santoso
authors.affiliation: Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Tode
authors.affiliation: Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Taizou
authors.initials: T
authors.lastname: Hirano
authors.affiliation: Department of Respiratory Medicine, Tohoku University Hospital, Sendai, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Ohkouchi
authors.affiliation: Department of Respiratory Medicine, Tohoku University Hospital, Sendai, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tamada
authors.affiliation: Department of Respiratory Medicine, Tohoku University Hospital, Sendai, Japan.
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Sugiura
authors.affiliation: Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Harigae
authors.affiliation: Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan Department of Respiratory Medicine, Tohoku University Hospital, Sendai, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ichinose
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D051526:Fibroblast Growth Factor 10 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C496463:FGF10 protein, human; D051526:Fibroblast Growth Factor 10; D014157:Transcription Factors