Abstract:
:As granulocyte-colony-stimulating factor (G-CSF)-induced mobilization of hematopoietic stem/progenitor cells (HSPCs) increases human serum levels of hepatocyte growth factor (HGF), our aim was to investigate the role of HGF and its receptor, c-Met, in the mobilization of HSPC. CD34(+) cells and leukocytes were isolated from the bone marrow (BM) of normal donors and the peripheral blood (PB) of patients mobilized with G-CSF and chemotherapy. Plasma HGF levels were evaluated by ELISA and HGF and c-Met expression by RT-PCR, fluorescence-activated cell sorter (FACS) analysis, and confocal microscopy. Because matrix metalloproteinases (MMPs) facilitate migration across extracellular matrix (ECM) and basement membranes, we also examined expression of MMP-9 and membrane type 1 (MT1)-MMP in hematopoietic cells after HGF stimulation. We found that plasma HGF levels in mobilized (m)PB were higher in patients who are good mobilizers and correlated with their white blood cell (WBC) and CD34(+) cell counts. Moreover, HGF and c-Met expression was significantly higher in mPB CD34(+) cells and leukocytes than in their steady-state BM counterpart cells and was up-regulated by G-CSF. Like G-CSF, HGF increased the secretion of MMP-9 and the expression of MT1-MMP in leukocytes, which was abrogated by the c-Met inhibitor K-252a. This inhibitor also significantly reduced the trans-Matrigel migration of mPB CD34(+) cells toward HGF. Our results suggest that G-CSF-mediated HSPC mobilization occurs in part through the HGF/c-Met axis in HSPC and myeloid cells, eliciting increased production of matrix-degrading enzymes and subsequently facilitating egress of HSPC.
journal_name
Stem Cells Devjournal_title
Stem cells and developmentauthors
Jalili A,Shirvaikar N,Marquez-Curtis LA,Turner AR,Janowska-Wieczorek Adoi
10.1089/scd.2009.0376subject
Has Abstractpub_date
2010-08-01 00:00:00pages
1143-51issue
8eissn
1547-3287issn
1557-8534journal_volume
19pub_type
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journal_title:Stem cells and development
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pub_type: 杂志文章,评审
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journal_title:Stem cells and development
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journal_title:Stem cells and development
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journal_title:Stem cells and development
pub_type: 杂志文章
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journal_title:Stem cells and development
pub_type: 社论
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journal_title:Stem cells and development
pub_type: 杂志文章
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journal_title:Stem cells and development
pub_type: 杂志文章
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journal_title:Stem cells and development
pub_type: 杂志文章
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journal_title:Stem cells and development
pub_type: 杂志文章
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journal_title:Stem cells and development
pub_type: 杂志文章,评审
doi:10.1089/scd.2010.0223
更新日期:2011-01-01 00:00:00
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journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2009.0224
更新日期:2010-06-01 00:00:00
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journal_title:Stem cells and development
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doi:10.1089/scd.2010.0494
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pub_type: 杂志文章
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journal_title:Stem cells and development
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journal_title:Stem cells and development
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journal_title:Stem cells and development
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