title: Mesenchymal stem cells inhibit multiple myeloma cells via the Fas/Fas ligand pathway.
abstract: BACKGROUND
  Cell-based therapy represents a new frontier in the treatment of a wide variety of human diseases traditionally associated with morbidity outcomes, including those involving inflammation, autoimmunity, tissue damage, and cancer. However, the use of mesenchymal stem cells (MSCs) to treat multiple myeloma (MM) bone disease has raised concerns. Specifically, evidence has shown that infused MSCs might support tumor growth and metastasis.
  
  
  METHODS
  In this study, we used a standard disseminated MM model in mice to identify the in vivo effects of intravenous MSC infusion. In addition, a series of in vitro co-culture assays were preformed to explore whether Fas/Fas ligand (Fas-L) is involved in the inhibitory effects of MSCs on MM cells.
  
  
  RESULTS
  In the MM mouse model, treatment of MSCs with highly expressed Fas ligand (Fas-L high MSCs) showed remarkable inhibitory effects on MM indenization in terms of extending the mouse survival rate and inhibiting tumor growth, bone resorption in the lumbus and collum femoris, and MM cell metastasis in the lungs and kidneys. In addition, reduced proliferation and increased apoptosis of MM cells was observed when co-cultured with Fas-L high MSCs in vitro. Furthermore, mechanistically, the binding between Fas and Fas-L significantly induced apoptosis in MM cells, as evidenced through an increase in the expression of apoptosis marker and Fas in MM cells. In contrast, Fas-L null MSCs promote MM growth.
  
  
  CONCLUSIONS
  These data suggest that Fas/Fas-L-induced MM apoptosis plays a crucial role in the MSC-based inhibition of MM growth. Although whether MSCs inhibit or promote cancer growth remains controversial, the levels of Fas-L expression in MSCs determine, at least partially, the effects of MSCs on MM cell growth.
authors.forename: Ikiru
authors.initials: I
authors.lastname: Atsuta
authors.forename: Shiyu
authors.initials: S
authors.lastname: Liu
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miura
authors.forename: Kentaro
authors.initials: K
authors.lastname: Akiyama
authors.forename: Chider
authors.initials: C
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: An
authors.forename: Songtao
authors.initials: S
authors.lastname: Shi
authors.forename: Fa-Ming
authors.initials: FM
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis; D001842:Bone and Bones / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D053222:Fas Ligand Protein / Q000378:metabolism*; D005260:Female; D007680:Kidney Neoplasms / Q000473:pathology / Q000556:secondary; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009101:Multiple Myeloma / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D015398:Signal Transduction; D015996:Survival Rate; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D053222:Fas Ligand Protein; C491899:Fas protein, mouse; D019014:fas Receptor
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