title: Tumor stroma engraftment of gene-modified mesenchymal stem cells as anti-tumor therapy against ovarian cancer.
abstract: OBJECTIVE
  Many ovarian cancers originate from ovarian surface epithelium, where they develop from cysts intermixed with stroma. The stromal layer is critical to the progression and survival of the neoplasm and consequently is recruited into the tumor microenvironment.
  
  
  METHODS
  Using both syngeneic mouse tumors (ID8-R) and human xenograft (OVCAR3, SKOV3) tumor models, we first confirmed that intraperitoneally injected circulating mesenchymal stem cells (MSCs) could target, preferentially engraft and differentiate into α-smooth muscle actin-positive myofibroblasts, suggesting their role as "reactive stroma" in ovarian carcinoma development and confirming their potential as a targeted delivery vehicle for the intratumoral production of interferon-β (IFN-β). Mice with ovarian carcinomas then received weekly intraperitoneal injections of IFN-β expressing MSCs.
  
  
  RESULTS
  Intraperitoneal injections of IFN-β expressing MSCs resulted in complete eradication of tumors in 70% of treated OVCAR3 mice (P = 0.004) and an increased survival of treated SKOV3 mice compared with controls (P = 0.01). Similar tumor growth control was observed using murine IFN-β delivered by murine MSCs in ID8-R ovarian carcinoma. As a potential mechanism of tumor killing, MSCs produced IFN-β-induced caspase-dependent tumor cell apoptosis.
  
  
  CONCLUSIONS
  Our results demonstrate that ovarian carcinoma engrafts MSCs to participate in myofibrovascular networks and that IFN-β produced by MSCs intratumorally modulates tumor kinetics, resulting in prolonged survival.
authors.affiliation: Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Dembinski
authors.forename: Shanna M
authors.initials: SM
authors.lastname: Wilson
authors.forename: Erika L
authors.initials: EL
authors.lastname: Spaeth
authors.forename: Matus
authors.initials: M
authors.lastname: Studeny
authors.forename: Claudia
authors.initials: C
authors.lastname: Zompetta
authors.forename: Ismael
authors.initials: I
authors.lastname: Samudio
authors.forename: Katherine
authors.initials: K
authors.lastname: Roby
authors.forename: Michael
authors.initials: M
authors.lastname: Andreeff
authors.forename: Frank C
authors.initials: FC
authors.lastname: Marini
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007150:Immunohistochemistry; D016899:Interferon-beta / Q000627:therapeutic use; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D010051:Ovarian Neoplasms / Q000628:therapy*; D023041:Xenograft Model Antitumor Assays
chemical_list: D016899:Interferon-beta