Abstract
Migratory capacity is a fundamental property of hematopoietic stem and progenitor cells (HSPCs). This feature is employed in clinical mobilization of HSPCs to the circulation and constitutes the basis for modern bone marrow (BM) transplantation procedures which are routinely used to treat hematological malignancies. Therefore, characterization of new players in the complex process of HSPC motility in steady-state conditions as well as during stress situations is a major challenge. We report that while the metalloproteinase membrane type 1-metalloprotease (MT1-MMP) has an essential role in human HSPC trafficking during granulocyte colony-stimulating factor (G-CSF)-induced mobilization, its inhibitor reversion-inducing cysteine-rich protein with Kazal motifs (RECK) and the adhesion molecule CD44 are required for HSPC retention to the BM in steady-state conditions. The nervous system via Wnt signaling along with HGF/c-Met signaling and the complement cascade play a major role in regulating MT1-MMP increased activity, CD44 cleavage, and RECK-reduced expression during G-CSF-induced mobilization. This review will elaborate on the opposite roles of MT1-MMP and RECK in HSPC migration and retention and suggest targeting them in order to facilitate HSPC mobilization and engraftment upon BM transplantation in patients.
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Lapidot T, Kollet O (2010) The brain-bone-blood triad: traffic lights for stem-cell homing and mobilization. Hematology Am Soc Hematol Educ Program 2010:1–6
Spiegel A, Kalinkovich A, Shivtiel S, Kollet O, Lapidot T (2008) Stem cell regulation via dynamic interactions of the nervous and immune systems with the microenvironment. Cell Stem Cell 3:484–492
Hoggatt J, Pelus LM (2011) Many mechanisms mediating mobilization: an alliterative review. Curr Opin Hematol 18:231–238
Greenbaum AM, Link DC (2011) Mechanisms of G-CSF-mediated hematopoietic stem and progenitor mobilization. Leukemia 25:211–217
Lapidot T, Petit I (2002) Current understanding of stem cell mobilization: the roles of chemokines, proteolytic enzymes, adhesion molecules, cytokines, and stromal cells. Exp Hematol 30:973–981
Nervi B, Link DC, DiPersio JF (2006) Cytokines and hematopoietic stem cell mobilization. J Cell Biochem 99:690–705
Kollet O, Dar A, Lapidot T (2007) The multiple roles of osteoclasts in host defense: bone remodeling and hematopoietic stem cell mobilization. Annu Rev Immunol 25:51–69
Mendez-Ferrer S, Lucas D, Battista M, Frenette PS (2008) Haematopoietic stem cell release is regulated by circadian oscillations. Nature 452:442–447
Spiegel A, Shivtiel S, Kalinkovich A, Ludin A, Netzer N, Goichberg P, Azaria Y, Resnick I, Hardan I, Ben-Hur H, Nagler A, Rubinstein M, Lapidot T (2007) Catecholaminergic neurotransmitters regulate migration and repopulation of immature human CD34+ cells through Wnt signaling. Nat Immunol 8:1123–1131
Katayama Y, Battista M, Kao WM, Hidalgo A, Peired AJ, Thomas SA, Frenette PS (2006) Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow. Cell 124:407–421
Kalinkovich A, Spiegel A, Shivtiel S, Kollet O, Jordaney N, Piacibello W, Lapidot T (2009) Blood-forming stem cells are nervous: direct and indirect regulation of immature human CD34+ cells by the nervous system. Brain Behav Immun 23:1059–1065
Abkowitz JL, Robinson AE, Kale S, Long MW, Chen J (2003) Mobilization of hematopoietic stem cells during homeostasis and after cytokine exposure. Blood 102:1249–1253
Wright DE, Wagers AJ, Gulati AP, Johnson FL, Weissman IL (2001) Physiological migration of hematopoietic stem and progenitor cells. Science 294:1933–1936
Greenbaum AM, Link DC (2011) Mechanisms of G-CSF-mediated hematopoietic stem and progenitor mobilization. Leukemia 25(2):211–217
Papayannopoulou T, Scadden DT (2008) Stem-cell ecology and stem cells in motion. Blood 111:3923–3930
Levesque JP, Takamatsu Y, Nilsson SK, Haylock DN, Simmons PJ (2001) Vascular cell adhesion molecule-1 (CD106) is cleaved by neutrophil proteases in the bone marrow following hematopoietic progenitor cell mobilization by granulocyte colony-stimulating factor. Blood 98:1289–1297
Peled A, Petit I, Kollet O, Magid M, Ponomaryov T, Byk T, Nagler A, Ben-Hur H, Many A, Shultz L, Lider O, Alon R, Zipori D, Lapidot T (1999) Dependence of human stem cell engraftment and repopulation of NOD/SCID mice on CXCR4. Science 283:845–848
Wright N, Hidalgo A, Rodriguez-Frade JM, Soriano SF, Mellado M, Parmo-Cabanas M, Briskin MJ, Teixido J (2002) The chemokine stromal cell-derived factor-1 alpha modulates alpha 4 beta 7 integrin-mediated lymphocyte adhesion to mucosal addressin cell adhesion molecule-1 and fibronectin. J Immunol 168:5268–5277
Dar A, Kollet O, Lapidot T (2006) Mutual, reciprocal SDF-1/CXCR4 interactions between hematopoietic and bone marrow stromal cells regulate human stem cell migration and development in NOD/SCID chimeric mice. Exp Hematol 34:967–975
Lapidot T, Kollet O (2002) The essential roles of the chemokine SDF-1 and its receptor CXCR4 in human stem cell homing and repopulation of transplanted immune-deficient NOD/SCID and NOD/SCID/B2m(null) mice. Leukemia 16:1992–2003
Dar A, Schajnovitz A, Lapid K, Kalinkovich A, Itkin T, Ludin A, Kao WM, Battista M, Tesio M, Kollet O, Cohen NN, Margalit R, Buss EC, Baleux F, Oishi S, Fujii N, Larochelle A, Dunbar CE, Broxmeyer HE, Frenette PS, Lapidot T (2011) Rapid mobilization of hematopoietic progenitors by AMD3100 and catecholamines is mediated by CXCR4-dependent SDF-1 release from bone marrow stromal cells. Leukemia doi:10.1038/leu.2011.62
Levesque JP, Hendy J, Winkler IG, Takamatsu Y, Simmons PJ (2003) Granulocyte colony-stimulating factor induces the release in the bone marrow of proteases that cleave c-KIT receptor (CD117) from the surface of hematopoietic progenitor cells. Exp Hematol 31:109–117
Petit I, Szyper-Kravitz M, Nagler A, Lahav M, Peled A, Habler L, Ponomaryov T, Taichman RS, Arenzana-Seisdedos F, Fujii N, Sandbank J, Zipori D, Lapidot T (2002) G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4. Nat Immunol 3:687–694
Semerad CL, Christopher MJ, Liu F, Short B, Simmons PJ, Winkler I, Levesque JP, Chappel J, Ross FP, Link DC (2005) G-CSF potently inhibits osteoblast activity and CXCL12 mRNA expression in the bone marrow. Blood 106:3020–3027
Sugiyama T, Kohara H, Noda M, Nagasawa T (2006) Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity 25:977–988
Nie YC, Han YC, Zou YR (2008) CXCR4 is required for the quiescence of primitive hematopoietic cells. J Exp Med 205:777–783
Hadler-Olsen E, Fadnes B, Sylte I, Uhlin-Hansen L, Winberg JO (2011) Regulation of matrix metalloproteinase activity in health and disease. FEBS J 278:28–45
Page-McCaw A, Ewald AJ, Werb Z (2007) Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol 8:221–233
Parks WC, Wilson CL, Lopez-Boado YS (2004) Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat Rev Immunol 4:617–629
Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2:161–174
Nagase H, Visse R, Murphy G (2006) Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res 69:562–573
Itoh Y, Seiki M (2006) MT1-MMP: a potent modifier of pericellular microenvironment. J Cell Physiol 206:1–8
Sato H, Takino T (2010) Coordinate action of membrane-type matrix metalloproteinase-1 (MT1-MMP) and MMP-2 enhances pericellular proteolysis and invasion. Cancer Sci 101:843–847
Strongin AY (2010) Proteolytic and non-proteolytic roles of membrane type-1 matrix metalloproteinase in malignancy. Biochim Biophys Acta 1803:133–141
Holmbeck K, Bianco P, Caterina J, Yamada S, Kromer M, Kuznetsov SA, Mankani M, Robey PG, Poole AR, Pidoux I, Ward JM, Birkedal-Hansen H (1999) MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover. Cell 99:81–92
Zhou Z, Apte SS, Soininen R, Cao R, Baaklini GY, Rauser RW, Wang J, Cao Y, Tryggvason K (2000) Impaired endochondral ossification and angiogenesis in mice deficient in membrane-type matrix metalloproteinase I. Proc Natl Acad Sci USA 97:4052–4057
Sakr MA, Takino T, Domoto T, Nakano H, Wong RW, Sasaki M, Nakanuma Y, Sato H (2010) GI24 enhances tumor invasiveness by regulating cell surface membrane-type 1 matrix metalloproteinase. Cancer Sci 101:2368–2374
Poincloux R, Lizarraga F, Chavrier P (2009) Matrix invasion by tumour cells: a focus on MT1-MMP trafficking to invadopodia. J Cell Sci 122:3015–3024
Matias-Roman S, Galvez BG, Genis L, Yanez-Mo M, de la Rosa G, Sanchez-Mateos P, Sanchez-Madrid F, Arroyo AG (2005) Membrane type 1-matrix metalloproteinase is involved in migration of human monocytes and is regulated through their interaction with fibronectin or endothelium. Blood 105:3956–3964
Ries C, Egea V, Karow M, Kolb H, Jochum M, Neth P (2007) MMP-2, MT1-MMP, and TIMP-2 are essential for the invasive capacity of human mesenchymal stem cells: differential regulation by inflammatory cytokines. Blood 109:4055–4063
Son BR, Marquez-Curtis LA, Kucia M, Wysoczynski M, Turner AR, Ratajczak J, Ratajczak MZ, Janowska-Wieczorek A (2006) Migration of bone marrow and cord blood mesenchymal stem cells in vitro is regulated by stromal-derived factor-1-CXCR4 and hepatocyte growth factor-c-met axes and involves matrix metalloproteinases. Stem Cells 24:1254–1264
Endo K, Takino T, Miyamori H, Kinsen H, Yoshizaki T, Furukawa M, Sato H (2003) Cleavage of syndecan-1 by membrane type matrix metalloproteinase-1 stimulates cell migration. J Biol Chem 278:40764–40770
Takahashi C, Sheng Z, Horan TP, Kitayama H, Maki M, Hitomi K, Kitaura Y, Takai S, Sasahara RM, Horimoto A, Ikawa Y, Ratzkin BJ, Arakawa T, Noda M (1998) Regulation of matrix metalloproteinase-9 and inhibition of tumor invasion by the membrane-anchored glycoprotein RECK. Proc Natl Acad Sci USA 95:13221–13226
Oh J, Takahashi R, Kondo S, Mizoguchi A, Adachi E, Sasahara RM, Nishimura S, Imamura Y, Kitayama H, Alexander DB, Ide C, Horan TP, Arakawa T, Yoshida H, Nishikawa S, Itoh Y, Seiki M, Itohara S, Takahashi C, Noda M (2001) The membrane-anchored MMP inhibitor RECK is a key regulator of extracellular matrix integrity and angiogenesis. Cell 107:789–800
Noda M, Oh J, Takahashi R, Kondo S, Kitayama H, Takahashi C (2003) RECK: a novel suppressor of malignancy linking oncogenic signaling to extracellular matrix remodeling. Cancer Metastasis Rev 22:167–175
Vagima Y, Avigdor A, Goichberg P, Shivtiel S, Tesio M, Kalinkovich A, Golan K, Dar A, Kollet O, Petit I, Perl O, Rosenthal E, Resnick I, Hardan I, Gellman YN, Naor D, Nagler A, Lapidot T (2009) MT1-MMP and RECK are involved in human CD34+ progenitor cell retention, egress, and mobilization. J Clin Invest 119:492–503
Shirvaikar N, Marquez-Curtis LA, Shaw AR, Turner AR, Janowska-Wieczorek A (2010) MT1-MMP association with membrane lipid rafts facilitates G-CSF-induced hematopoietic stem/progenitor cell mobilization. Exp Hematol 38:823–835
Wysoczynski M, Reca R, Ratajczak J, Kucia M, Shirvaikar N, Honczarenko M, Mills M, Wanzeck J, Janowska-Wieczorek A, Ratajczak MZ (2005) Incorporation of CXCR4 into membrane lipid rafts primes homing-related responses of hematopoietic stem/progenitor cells to an SDF-1 gradient. Blood 105:40–48
Ratajczak MZ, Lee H, Wysoczynski M, Wan W, Marlicz W, Laughlin MJ, Kucia M, Janowska-Wieczorek A, Ratajczak J (2010) Novel insight into stem cell mobilization-plasma sphingosine-1-phosphate is a major chemoattractant that directs the egress of hematopoietic stem progenitor cells from the bone marrow and its level in peripheral blood increases during mobilization due to activation of complement cascade/membrane attack complex. Leukemia 24:976–985
Golan K VY, Ludin A, Itkin T, Kalinkovich A, Cohen-Gur S, Kollet O, Schajnovitz A, Shivtiel S, Lapidot T (2010) The chemotactic lipid S1P regulates hematopoietic progenitor cell egress and mobilization via its major receptor S1P1 and by SDF-1 inhibition in a p38/Akt/mTOR dependent manner [abstract no. 553]. Blood 116
Harun N TM, Juarez JG, Bradstock KF, Bendall LJ (2010) S1P1 Agonists for use as adjunct mobilizing agents [abstract no. 826]. Blood 116
Zhang J, Grindley JC, Yin T, Jayasinghe S, He XC, Ross JT, Haug JS, Rupp D, Porter-Westpfahl KS, Wiedemann LM, Wu H, Li L (2006) PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention. Nature 441:518–522
Trusolino L, Comoglio PM (2002) Scatter-factor and semaphorin receptors: cell signalling for invasive growth. Nat Rev Cancer 2:289–300
Tesio M, Golan K, Corso S, Giordano S, Schajnovitz A, Vagima Y, Shivtiel S, Kalinkovich A, Caione L, Gammaitoni L, Laurenti E, Buss EC, Shezen E, Itkin T, Kollet O, Petit I, Trumpp A, Christensen J, Aglietta M, Piacibello W, Lapidot T (2011) Enhanced c-Met activity promotes G-CSF-induced mobilization of hematopoietic progenitor cells via ROS signaling. Blood 117:419–428
Levesque JP, Winkler IG, Hendy J, Williams B, Helwani F, Barbier V, Nowlan B, Nilsson SK (2007) Hematopoietic progenitor cell mobilization results in hypoxia with increased hypoxia-inducible transcription factor-1 alpha and vascular endothelial growth factor A in bone marrow. Stem Cells 25:1954–1965
Jalili A, Shirvaikar N, Marquez-Curtis LA, Turner AR, Janowska-Wieczorek A (2010) The HGF/c-Met axis synergizes with G-CSF in the mobilization of hematopoietic stem/progenitor cells. Stem Cells Dev 19:1143–1151
Kollet O, Dar A, Shivtiel S, Kalinkovich A, Lapid K, Sztainberg Y, Tesio M, Samstein RM, Goichberg P, Spiegel A, Elson A, Lapidot T (2006) Osteoclasts degrade endosteal components and promote mobilization of hematopoietic progenitor cells. Nat Med 12:657–664
Reca R, Cramer D, Yan J, Laughlin MJ, Janowska-Wieczorek A, Ratajczak J, Ratajczak MZ (2007) A novel role of complement in mobilization: immunodeficient mice are poor granulocyte-colony stimulating factor mobilizers because they lack complement-activating immunoglobulins. Stem Cells 25:3093–3100
Jalili A, Shirvaikar N, Marquez-Curtis L, Qiu Y, Korol C, Lee H, Turner AR, Ratajczak MZ, Janowska-Wieczorek A (2010) Fifth complement cascade protein (C5) cleavage fragments disrupt the SDF-1/CXCR4 axis: further evidence that innate immunity orchestrates the mobilization of hematopoietic stem/progenitor cells. Exp Hematol 38:321–332
Prosper F, Verfaillie CM (2001) Regulation of hematopoiesis through adhesion receptors. J Leukoc Biol 69:307–316
Avigdor A, Goichberg P, Shivtiel S, Dar A, Peled A, Samira S, Kollet O, Hershkoviz R, Alon R, Hardan I, Ben-Hur H, Naor D, Nagler A, Lapidot T (2004) CD44 and hyaluronic acid cooperate with SDF-1 in the trafficking of human CD34+ stem/progenitor cells to bone marrow. Blood 103:2981–2989
Voermans C, Kooi ML, Rodenhuis S, van der Lelie H, van der Schoot CE, Gerritsen WR (2001) In vitro migratory capacity of CD34+ cells is related to hematopoietic recovery after autologous stem cell transplantation. Blood 97:799–804
Wright DE, Bowman EP, Wagers AJ, Butcher EC, Weissman IL (2002) Hematopoietic stem cells are uniquely selective in their migratory response to chemokines. J Exp Med 195:1145–1154
Lee HM, Wu W, Wysoczynski M, Liu R, Zuba-Surma EK, Kucia M, Ratajczak J, Ratajczak MZ (2009) Impaired mobilization of hematopoietic stem/progenitor cells in C5-deficient mice supports the pivotal involvement of innate immunity in this process and reveals novel promobilization effects of granulocytes. Leukemia 23:2052–2062
Ratajczak J, Reca R, Kucia M, Majka M, Allendorf DJ, Baran JT, Janowska-Wieczorek A, Wetsel RA, Ross GD, Ratajczak MZ (2004) Mobilization studies in mice deficient in either C3 or C3a receptor (C3aR) reveal a novel role for complement in retention of hematopoietic stem/progenitor cells in bone marrow. Blood 103:2071–2078
Mohle R, Haas R, Hunstein W (1993) Expression of adhesion molecules and c-kit on CD34+ hematopoietic progenitor cells: comparison of cytokine-mobilized blood stem cells with normal bone marrow and peripheral blood. J Hematother 2:483–489
Pruijt JFM, Fibbe WE, Laterveer L, Pieters RA, Lindley IJD, Paemen L, Masure S, Willemze R, Opdenakker G (1999) Prevention of interleukin-8-induced mobilization of hematopoietic progenitor cells in rhesus monkeys by inhibitory antibodies against the metalloproteinase gelatinase B (MMP-9). Proc Natl Acad Sci USA 96:10863–10868
Choi JH, Han EH, Hwang YP, Choi JM, Choi CY, Chung YC, Seo JK, Jeong HG (2010) Suppression of PMA-induced tumor cell invasion and metastasis by aqueous extract isolated from Prunella vulgaris via the inhibition of NF-kappaB-dependent MMP-9 expression. Food Chem Toxicol 48:564–571
Hamsa TP, Kuttan G (2011) Inhibition of invasion and experimental metastasis of murine melanoma cells by Ipomoea obscura (L.) is mediated through the down-regulation of inflammatory mediators and matrix-metalloproteinases. J Exp Ther Oncol 9:139–151
Wang C, Chen Z, Li Z, Cen J (2010) The essential roles of matrix metalloproteinase-2, membrane type 1 metalloproteinase and tissue inhibitor of metalloproteinase-2 in the invasive capacity of acute monocytic leukemia SHI-1 cells. Leuk Res 34:1083–1090
Creutzig U, Harbott J, Sperling C, Ritter J, Zimmermann M, Loffler H, Riehm H, Schellong G, Ludwig WD (1995) Clinical significance of surface antigen expression in children with acute myeloid leukemia: results of study AML-BFM-87. Blood 86:3097–3108
Ravindranath Y, Steuber CP, Krischer J, Civin CI, Ducore J, Vega R, Pitel P, Inoue S, Bleher E, Sexauer C et al (1991) High-dose cytarabine for intensification of early therapy of childhood acute myeloid leukemia: a Pediatric Oncology Group study. J Clin Oncol 9:572–580
Chang H, Brandwein J, Yi QL, Chun K, Patterson B, Brien B (2004) Extramedullary infiltrates of AML are associated with CD56 expression, 11q23 abnormalities and inferior clinical outcome. Leuk Res 28:1007–1011
Rubnitz JE, Raimondi SC, Halbert AR, Tong X, Srivastava DK, Razzouk BI, Pui CH, Downing JR, Ribeiro RC, Behm FG (2002) Characteristics and outcome of t(8;21)-positive childhood acute myeloid leukemia: a single institution’s experience. Leukemia 16:2072–2077
Murai R, Yoshida Y, Muraguchi T, Nishimoto E, Morioka Y, Kitayama H, Kondoh S, Kawazoe Y, Hiraoka M, Uesugi M, Noda M (2010) A novel screen using the Reck tumor suppressor gene promoter detects both conventional and metastasis-suppressing anticancer drugs. Oncotarget 1:252–264
Suojanen J, Salo T, Koivunen E, Sorsa T, Pirila E (2009) A novel and selective membrane type-1 matrix metalloproteinase (MT1-MMP) inhibitor reduces cancer cell motility and tumor growth. Cancer Biol Ther 8:2362–2370
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Golan, K., Vagima, Y., Goichberg, P. et al. MT1-MMP and RECK: opposite and essential roles in hematopoietic stem and progenitor cell retention and migration. J Mol Med 89, 1167–1174 (2011). https://doi.org/10.1007/s00109-011-0792-9
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DOI: https://doi.org/10.1007/s00109-011-0792-9