PMID- 24304929
OWN - NLM
STAT- MEDLINE
DCOM- 20140926
LR  - 20220316
IS  - 1479-5876 (Electronic)
IS  - 1479-5876 (Linking)
VI  - 11
DP  - 2013 Dec 4
TI  - Leukemia cells induce changes in human bone marrow stromal cells.
PG  - 298
LID - 10.1186/1479-5876-11-298 [doi]
AB  - BACKGROUND: Bone marrow stromal cells (BMSCs) are multipotent cells that support 
      angiogenesis, wound healing, and immunomodulation. In the hematopoietic niche, 
      they nurture hematopoietic cells, leukemia, tumors and metastasis. BMSCs secrete 
      of a wide range of cytokines, growth factors and matrix proteins which contribute 
      to the pro-tumorigenic marrow microenvironment. The inflammatory cytokines IFN-gamma 
      and TNF-alpha change the BMSC secretome and we hypothesized that factors produced by 
      tumors or leukemia would also affect the BMSC secretome and investigated the 
      interaction of leukemia cells with BMSCs. METHODS: BMSCs from healthy subjects 
      were co-cultured with three myeloid leukemia cell lines (TF-1, TF-1alpha and K562) 
      using a trans-well system. Following co-culture, the BMSCs and leukemia cells 
      were analyzed by global gene expression analysis and culture supernatants were 
      analyzed for protein expression. As a control, CD34+ cells were also cocultured 
      with BMSCs. RESULTS: Co-culture induced leukemia cell gene expression changes in 
      stem cell pluripotency, TGF-beta signaling and carcinoma signaling pathways. BMSCs 
      co-cultured with leukemia cells up-regulated a number of proinflammatory genes 
      including IL-17 signaling-related genes and IL-8 and CCL2 levels were increased 
      in co-culture supernatants. In contrast, purine metabolism, mTOR signaling and 
      EIF2 signaling pathways genes were up-regulated in BMSCs co-cultured with CD34+ 
      cells. CONCLUSIONS: BMSCs react to the presence of leukemia cells undergoing 
      changes in the cytokine and chemokine secretion profiles. Thus, BMSCs and 
      leukemia cells both contribute to the creation of a competitive niche more 
      favorable for leukemia stem cells.
FAU - Civini, Sara
AU  - Civini S
FAU - Jin, Ping
AU  - Jin P
FAU - Ren, Jiaqiang
AU  - Ren J
FAU - Sabatino, Marianna
AU  - Sabatino M
FAU - Castiello, Luciano
AU  - Castiello L
FAU - Jin, Jianjian
AU  - Jin J
FAU - Wang, Huan
AU  - Wang H
FAU - Zhao, Yuanlong
AU  - Zhao Y
FAU - Marincola, Francesco
AU  - Marincola F
FAU - Stroncek, David
AU  - Stroncek D
AD  - Cell Processing Section, Department of Transfusion Medicine, Clinical Center, 
      National Institutes of Health (NIH), Building 10, Room 3C720, 9000 Rockville 
      Pike, Bethesda, MD 20892-1184, USA. DStroncek@cc.nih.gov.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20131204
PL  - England
TA  - J Transl Med
JT  - Journal of translational medicine
JID - 101190741
SB  - IM
MH  - Bone Marrow Cells/metabolism/*pathology
MH  - Coculture Techniques
MH  - Gene Expression Profiling
MH  - Humans
MH  - Leukemia/genetics/metabolism/*pathology
MH  - Stromal Cells/metabolism/*pathology
PMC - PMC3882878
EDAT- 2013/12/07 06:00
MHDA- 2014/09/27 06:00
PMCR- 2013/12/04
CRDT- 2013/12/06 06:00
PHST- 2013/11/25 00:00 [received]
PHST- 2013/11/27 00:00 [accepted]
PHST- 2013/12/06 06:00 [entrez]
PHST- 2013/12/07 06:00 [pubmed]
PHST- 2014/09/27 06:00 [medline]
PHST- 2013/12/04 00:00 [pmc-release]
AID - 1479-5876-11-298 [pii]
AID - 10.1186/1479-5876-11-298 [doi]
PST - epublish
SO  - J Transl Med. 2013 Dec 4;11:298. doi: 10.1186/1479-5876-11-298.