@article{10.1172/JCI36541, author = {Yaron Vagima AND Abraham Avigdor AND Polina Goichberg AND Shoham Shivtiel AND Melania Tesio AND Alexander Kalinkovich AND Karin Golan AND Ayelet Dar AND Orit Kollet AND Isabelle Petit AND Orly Perl AND Ester Rosenthal AND Igor Resnick AND Izhar Hardan AND Yechiel N. Gellman AND David Naor AND Arnon Nagler AND Tsvee Lapidot}, journal = {The Journal of Clinical Investigation}, publisher = {The American Society for Clinical Investigation}, title = {MT1-MMP and RECK are involved in human CD34+ progenitor cell retention, egress, and mobilization}, year = {2009}, month = {3}, volume = {119}, url = {https://www.jci.org/articles/view/36541}, pages = {492-503}, abstract = {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.}, number = {3}, doi = {10.1172/JCI36541}, url = {https://doi.org/10.1172/JCI36541}, }