التفاصيل البيبلوغرافية
| العنوان: |
MT1-MMP and RECK are involved in human CD34+ progenitor cell retention, egress, and mobilization. |
| المؤلفون: |
Vagima, Yaron1, Avigdor, Abraham1,2, Goichberg, Polina1, Shivtiel, Shoham1, Tesio, Melania1, Kalinkovich, Alexander1, Golan, Karin1, Dar, Ayelet1, Kollet, Orit1, Petit, Isabelle1, Perl, Orly2, Rosenthal, Ester2, Resnick, Igor3, Hardan, Izhar2, Gellman, Yechiel N.4, Naor, David4, Nagler, Arnon2, Lapidot, Tsvee1 tsvee.lapidot@weizmann.ac.il |
| المصدر: |
Journal of Clinical Investigation. Mar2009, Vol. 119 Issue 3, p492-503. 12p. 1 Diagram, 7 Graphs. |
| مصطلحات موضوعية: |
*PROTEINS, *CANCER, *SMALL interfering RNA, *CHEMOTAXIS, *LABORATORY mice |
| مستخلص: |
The mechanisms governing hematopoietic progenitor cell mobilization are not fully understood. We report higher membrane type 1-MMP (MT1-MMP) and lower expression of the MT1-MMP inhibitor, reversion-inducing cysteine-rich protein with Kazal motifs (RECK), on isolated circulating human CD34+ progenitor cells compared with immature BM cells. The expression of MT1-MMP correlated with clinical mobilization of CD34+ cells in healthy donors and patients with lymphoid malignancies. Treatment with G-CSF further increased MT1-MMP and decreased RECK expression in human and murine hematopoietic cells in a PI3K/Akt-dependent manner, resulting in elevated MT1-MMP activity. Blocking MT1-MMP function by Abs or siRNAs impaired chemotaxis and homing of G-CSF-mobilized human CD34+ progenitors. The mobilization of immature and maturing human progenitors in chimeric NOD/SCID mice by G-CSF was inhibited by anti-MT1-MMP treatment, while RECK neutralization promoted motility and egress of BM CD34+ cells. BM c-kit+ cells from MT1-MMP-deficient mice also exhibited inferior chemotaxis, reduced homing and engraftment capacities, and impaired G-CSF-induced mobilization in murine chimeras. Membranal CD44 cleavage by MT1-MMP was enhanced following G-CSF treatment, reducing CD34+ cell adhesion. Accordingly, CD44-deficient mice had a higher frequency of circulating progenitors. Our results reveal that the motility, adhesion, homing, and mobilization of human hematopoietic progenitor cells are regulated in a cell-autonomous manner by dynamic and opposite changes in MT1-MMP and RECK expression. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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