title: Myoblasts inhibit prostate cancer growth by paracrine secretion of tumor necrosis factor-α.
abstract: OBJECTIVE
  Myoblasts can form muscle fibers after transplantation. Therefore, they are envisioned as a treatment for urinary incontinence after radical prostatectomy. However, to our knowledge the safety of this treatment and the interaction of myoblasts with any remaining neighboring cancer are unknown. We investigated the interactions between myoblasts and prostate carcinoma cells in vitro and in vivo.
  
  
  METHODS
  Myoblasts isolated from the rectus abdominis were used in a series of co-culture experiments with prostate cancer cells and subcutaneously co-injected in vivo. Cell proliferation, cell cycle arrest and apoptosis of cancer in co-culture with myoblasts were assessed. Tumor volume and metastasis formation were evaluated in a mouse model. Tissue specific markers were assessed by immunohistochemistry, fluorescence activated cell sorting analysis, Western blot and real-time quantitative polymerase chain reaction.
  
  
  RESULTS
  Myoblasts in proximity to tumor provided paracrine tumor necrosis factor-α to their microenvironment, decreasing the tumor growth of all prostate cancer cell lines examined. Co-culture experiments revealed induction of cell cycle arrest, tumor death by apoptosis and increased myoblast differentiation. This effect was largely blocked by tumor necrosis factor-α inhibition. The same outcome was noted in a mouse model, in which co-injected human myoblasts also inhibited the tumor growth and metastasis formation of all prostate cancer cell lines evaluated.
  
  
  CONCLUSIONS
  Myoblasts restrict prostate cancer growth and limit metastasis formation by paracrine tumor necrosis factor-α secretion in vitro and in vivo.
authors.affiliation: Laboratory for Urologic Tissue Engineering and Stem Cell Therapy, Division of Urology, University of Zurich, Zürich, Switzerland.
authors.forename: Meline Nogueira Lucena
authors.initials: MN
authors.lastname: Stölting
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrari
authors.forename: Christoph
authors.initials: C
authors.lastname: Handschin
authors.forename: Attila
authors.initials: A
authors.lastname: Becskei
authors.forename: Maurizio
authors.initials: M
authors.lastname: Provenzano
authors.forename: Tullio
authors.initials: T
authors.lastname: Sulser
authors.forename: Daniel
authors.initials: D
authors.lastname: Eberli
mesh_terms: D000818:Animals; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D032446:Myoblasts / Q000502:physiology*; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000502:physiology
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha