title: p38 MAPK contributes to the growth inhibition of leukemic tumor cells mediated by human umbilical cord mesenchymal stem cells.
abstract: OBJECTIVE
  Mesenchymal stem cells (MSCs) have been implicated in antitumor therapy for hematopoietic and non-hematopoietic tumors. Cell-contact and soluble factors are demonstrated to play a role in the growth inhibition of tumor cells mediated by MSCs in vitro, while there is little clue about signaling pathways involved in the process. P38 MAPK has been implicated as a suppressor of cell proliferation and tumorigenesis. We here investigate whether p38 MAPK is involved in MSC-induced growth inhibition of leukemic tumor cells.
  
  
  METHODS
  We characterized the effect of human umbilical cord mesenchymal stem cells (UC-MSCs) on proliferation, cell cycle and phosphorylation pattern of p38 MAPK in HL60 and K562 cells. SB203580, a specific inhibitor of p38 MAPK, or p38 MAPK-small interfering RNA (siRNA), were used to identify the role of p38 in growth suppression by UC-MSCs. We also investigated the expression of cell cycle regulators.
  
  
  RESULTS
  Treatment with UC-MSCs led to potent proliferation-inhibition of HL60 and K562 cells without inducing apoptosis. Growth inhibition by UC-MSCs was due to G0/G1 arrest. UC-MSCs increased phosphorylation of p38 MAPK in HL60 and K562 cells. Pharmacological inhibition or genetic silencing (through siRNA) of p38 MAPK partially abrogated the proliferation-suppression and cell cycle arrest caused by UC-MSCs. UC-MSCs also modulated the expression of cell cycle regulatory proteins in HL60 and K562 cells while SB203580 reversed the effect.
  
  
  CONCLUSIONS
  Taken together, our findings indicate that p38 MAPK is critical for the growth inhibitory effect of UC-MSCs on leukemic tumor cells.
authors.affiliation: State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Tian
authors.forename: Shaoguang
authors.initials: S
authors.lastname: Yang
authors.forename: Qian
authors.initials: Q
authors.lastname: Ren
authors.forename: Zhibo
authors.initials: Z
authors.lastname: Han
authors.forename: Shihong
authors.initials: S
authors.lastname: Lu
authors.forename: Fengxia
authors.initials: F
authors.lastname: Ma
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Zhongchao
authors.initials: Z
authors.lastname: Han
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007938:Leukemia / Q000201:enzymology*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D014470:Umbilical Cord / Q000166:cytology
chemical_list: D018797:Cell Cycle Proteins; D007093:Imidazoles; D011725:Pyridines; D034741:RNA, Small Interfering; D048308:Mitogen-Activated Protein Kinase 14; C093642:SB 203580