title: A therapeutic strategy for metastatic malignant fibrous histiocytoma through mesenchymal stromal cell-mediated TRAIL production.
abstract: OBJECTIVE
  To overcome the therapeutic limitations of malignant fibrous histiocytoma (MFH), we evaluated human adipose tissue-derived mesenchymal stromal cells (MSCs) that secrete tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on metastatic MFH.
  
  
  BACKGROUND
  MFH is a highly malignant and metastatic type of sarcoma but surgical removal is the only effective method for treating MFH. MSCs are easily transduced to express a high level of transgene and can migrate toward cancer. For this reason, MSCs are a promising candidate for metastatic MFH therapies.
  
  
  METHODS
  In vitro sustainability of MSC-TRAIL against MFH-ino was analyzed by apoptosis assay. For preclinical study, anti-MFH effects of MSC-TRAILs were validated in murine models for local tumorigenesis and metastasis. Furthermore, a time-interval metastasis model of MFH was applied to confirm antimetastatic ability of MSC-TRAIL for preestablished metastatic MFH.
  
  
  RESULTS
  We found that MFH-ino is highly susceptible to recombinant TRAIL and MSC-TRAIL, which selectively induce apoptosis via caspase-8 activation in vitro. Moreover, not only MFH-ino but xenograft explants were also significantly inhibited by MSC-TRAIL in local tumorigenesis. In particular, the metastatic ability of MFH-ino was considerably reduced by MSC-TRAIL in metastasis murine model, particularly for preestablished metastatic MFH.
  
  
  CONCLUSIONS
  These results suggest that MSC-TRAIL is sufficiently effective in inhibiting MFH-ino metastasis and the application using MSC-TRAIL could be extended to other sarcomas and recurrent metastatic cancers for cell-mediated cancer therapy.
authors.affiliation: Transplantation Research Center, Samsung Biomedical Research Institute, Seoul, Republic of Korea.
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Heung-Mo
authors.initials: HM
authors.lastname: Yang
authors.forename: Young-Sil
authors.initials: YS
authors.lastname: Choi
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Park
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Moon
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Lee
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Sung
authors.forename: Sung Joo
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D052436:Adipose Tissue, White / Q000166:cytology*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D051677:Histiocytoma, Malignant Fibrous / Q000473:pathology / Q000628:therapy*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D009362:Neoplasm Metastasis; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D014161:Transduction, Genetic; D019076:Transgenes; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human