title: Bone marrow derived mesenchymal stem cells incorporate into the prostate during regrowth.
abstract: BACKGROUND
  Prostate cancer recurrence involves increased growth of cancer epithelial cells, as androgen dependent prostate cancer progresses to castrate resistant prostate cancer (CRPC) following initial therapy. Understanding CRPC prostate regrowth will provide opportunities for new cancer therapies to treat advanced disease.
  
  
  RESULTS
  Elevated chemokine expression in the prostate stroma of a castrate resistant mouse model, Tgfbr2(fspKO), prompted us to look at the involvement of bone marrow derived cells (BMDCs) in prostate regrowth. We identified bone marrow cells recruited to the prostate in GFP-chimeric mice. A dramatic increase in BMDC recruitment for prostate regrowth occurred three days after exogenous testosterone implantation. Recruitment led to incorporation of BMDCs within the prostate epithelia. Immunofluorescence staining suggested BMDCs in the prostate coexpressed androgen receptor; p63, a basal epithelial marker; and cytokeratin 8, a luminal epithelial marker. A subset of the BMDC population, mesenchymal stem cells (MSCs), were specifically found to be incorporated in the prostate at its greatest time of remodeling. Rosa26 expressing MSCs injected into GFP mice supported MSC fusion with resident prostate epithelial cells through co-localization of β-galactosidase and GFP during regrowth. In a human C4-2B xenograft model of CRPC, MSCs were specifically recruited. Injection of GFP-labeled MSCs supported C4-2B tumor progression by potentiating canonical Wnt signaling. The use of MSCs as a targeted delivery vector for the exogenously expressed Wnt antagonist, secreted frizzled related protein-2 (SFRP2), reduced tumor growth, increased apoptosis and potentiated tumor necrosis.
  
  
  CONCLUSIONS
  Mesenchymal stem cells fuse with prostate epithelia during the process of prostate regrowth. MSCs recruited to the regrowing prostate can be used as a vehicle for transporting genetic information with potential therapeutic effects on castrate resistant prostate cancer, for instance by antagonizing Wnt signaling through SFRP2.
authors.affiliation: Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee, United States of America.
authors.forename: Veronica R
authors.initials: VR
authors.lastname: Placencio
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Li
authors.forename: Taylor P
authors.initials: TP
authors.lastname: Sherrill
authors.forename: Gloria
authors.initials: G
authors.lastname: Fritz
authors.forename: Neil A
authors.initials: NA
authors.lastname: Bhowmick
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011467:Prostate / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000503:physiopathology; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C110853:Gt(ROSA)26Sor non-coding RNA, mouse; D011506:Proteins; D022661:RNA, Untranslated; D051153:Wnt Proteins