Enhanced c-Met activity promotes G-CSF–induced mobilization of hematopoietic progenitor cells via ROS signaling

Abstract Mechanisms governing stress-induced hematopoietic progenitor cell mobilization are not fully deciphered. We report that during granulocyte colony-stimulating factor–induced mobilization c-Met expression and signaling are up-regulated on immature bone marrow progenitors. Interestingly, stromal cell–derived factor 1/CXC chemokine receptor-4 signaling induced hepatocyte growth factor production and c-Met activation. We found that c-Met inhibition reduced mobilization of both immature progenitors and the more primitive Sca-1+/c-Kit+/Lin− cells and interfered with their enhanced chemotactic migration to stromal cell–derived factor 1. c-Met activation resulted in cellular accumulation of reactive oxygen species by mammalian target of rapamycin inhibition of Forkhead Box, subclass O3a. Blockage of mammalian target of rapamycin inhibition or reactive oxygen species signaling impaired c-Met–mediated mobilization. Our data show dynamic c-Met expression and function in the bone marrow and show that enhanced c-Met signaling is crucial to facilitate stress-induced mobilization of progenitor cells as part of host defense and repair mechanisms.

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The Effect of the Copper Chelator Tetraethylenepentamine on Reactive Oxygen Species Generation by Human Hematopoietic Progenitor Cells

Stem Cells and Development ◽

10.1089/scd.2007.0052 ◽

2007 ◽

Vol 16 (6) ◽

pp. 1053-1056 ◽

Cited By ~ 16

Author(s):

Eugenia Prus ◽

Eitan Fibach

Keyword(s):

Reactive Oxygen Species ◽

Progenitor Cells ◽

Reactive Oxygen Species Generation ◽

Reactive Oxygen ◽

Hematopoietic Progenitor Cells ◽

Oxygen Species ◽

Hematopoietic Progenitor ◽

Copper Chelator

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NADPH Oxidase–Generated Reactive Oxygen Species Are Required for Stromal Cell–Derived Factor-1α–Stimulated Angiogenesis

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.114.303733 ◽

2014 ◽

Vol 34 (9) ◽

pp. 2023-2032 ◽

Cited By ~ 22

Author(s):

Xinchun Pi ◽

Liang Xie ◽

Andrea L. Portbury ◽

Sarayu Kumar ◽

Pamela Lockyer ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Nadph Oxidase ◽

Stromal Cell ◽

Reactive Oxygen ◽

Oxygen Species ◽

Stromal Cell Derived Factor

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Celastrol prevents cadmium-induced neuronal cell death by blocking reactive oxygen species-mediated mammalian target of rapamycin pathway

British Journal of Pharmacology ◽

10.1111/bph.13655 ◽

2016 ◽

Vol 174 (1) ◽

pp. 82-100 ◽

Cited By ~ 16

Author(s):

Ruijie Zhang ◽

Nana Zhang ◽

Hai Zhang ◽

Chunxiao Liu ◽

Xiaoqing Dong ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Cell Death ◽

Neuronal Cell Death ◽

Mammalian Target Of Rapamycin ◽

Neuronal Cell ◽

Reactive Oxygen ◽

Target Of Rapamycin ◽

Oxygen Species

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Antimony, a novel nerve poison, triggers neuronal autophagic death via reactive oxygen species-mediated inhibition of the protein kinase B/mammalian target of rapamycin pathway

The International Journal of Biochemistry & Cell Biology ◽

10.1016/j.biocel.2019.105561 ◽

2019 ◽

Vol 114 ◽

pp. 105561 ◽

Cited By ~ 5

Author(s):

Xiaoke Wang ◽

Piaoyu Zhu ◽

Shenya Xu ◽

Yuting Liu ◽

Yang Jin ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Protein Kinase ◽

Protein Kinase B ◽

Mammalian Target Of Rapamycin ◽

Reactive Oxygen ◽

Target Of Rapamycin ◽

Oxygen Species

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The Chemokine Receptor CXCR-4 Is Expressed on CD34+Hematopoietic Progenitors and Leukemic Cells and Mediates Transendothelial Migration Induced by Stromal Cell-Derived Factor-1

Blood ◽

10.1182/blood.v91.12.4523 ◽

1998 ◽

Vol 91 (12) ◽

pp. 4523-4530 ◽

Cited By ~ 459

Author(s):

Robert Möhle ◽

Frank Bautz ◽

Shahin Rafii ◽

Malcolm A.S. Moore ◽

Wolfram Brugger ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Progenitor Cells ◽

Stromal Cell ◽

Leukemic Cell ◽

Transendothelial Migration ◽

Leukemic Cells ◽

Hematopoietic Progenitor ◽

Leukemic Cell Lines ◽

Stromal Cell Derived Factor

Abstract The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR-4 (fusin, LESTR) are likely to be involved in the trafficking of hematopoietic progenitor and stem cells, as suggested by the reduced bone marrow hematopoiesis in SDF-1–deficient mice and the chemotactic effect of SDF-1 on CD34+ progenitor cells. Migration of leukemic cells might also depend on the expression of chemokine receptors. Therefore, we analyzed expression of CXCR-4 on mobilized normal CD34+ progenitors and leukemic cells. In addition, SDF-1–induced transendothelial migration across a bone marrow endothelial cell layer was assessed in vitro. By flow cytometry, CXCR-4 was found to be expressed in significant amounts on circulating CD34+ hematopoietic progenitor cells, including more primitive subsets (CD34+/CD38− and CD34+/Thy-1+ cells). In accordance with the immunofluorescence data, CD34+ progenitors efficiently migrated across endothelium in response to SDF-1 containing conditioned medium from the stromal cell line MS-5. Leukemic blasts (mostly CD34+) from patients with acute myeloblastic leukemia (AML) expressed variable amounts of CXCR-4, which was functionally active, as demonstrated by a positive correlation between the SDF-1–induced transendothelial migration and the cell surface density of CXCR-4 (r = 0.97). Also recombinant SDF-1β induced migration of CXCR-4–positive leukemic blasts. The effect of both conditioned medium and recombinant SDF-1 was inhibited by a CXCR-4 blocking antibody. In contrast, CD34+ leukemic cell lines (KG1, KG1a, Kasumi-1, MOLM-1) expressed low levels or were negative for CXCR-4, and did not migrate. By reverse transcriptase-polymerase chain reaction (RT-PCR), however, basal levels of CXCR-4 mRNA were also detected in all leukemic cell lines. We conclude that CXCR-4 is expressed on CD34+cells including more primitive, pluripotent progenitors, and may therefore play a role in the homing of hematopoietic stem cells. CXCR-4 expressed in variable amounts on primary AML leukemic cells is functionally active and may be involved in the trafficking of malignant hematopoietic cells.

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Do vasculature reactive oxygen species play a role in the mobilization of bone marrow endothelial progenitor cells?

Journal of Hypertension ◽

10.1097/hjh.0b013e3282f2851a ◽

2008 ◽

Vol 26 (2) ◽

pp. 188-190 ◽

Cited By ~ 2

Author(s):

Hideyasu Kiyomoto ◽

Akira Nishiyama

Keyword(s):

Reactive Oxygen Species ◽

Bone Marrow ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Reactive Oxygen ◽

Oxygen Species ◽

Endothelial Progenitor

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Targeted release of stromal cell-derived factor-1α by reactive oxygen species-sensitive nanoparticles results in bone marrow stromal cell chemotaxis and homing, and repair of vascular injury caused by electrical burns

PLoS ONE ◽

10.1371/journal.pone.0194298 ◽

2018 ◽

Vol 13 (3) ◽

pp. e0194298 ◽

Cited By ~ 2

Author(s):

Fang He ◽

Peng-Fei Luo ◽

Tao Tang ◽

Fang Zhang ◽

He Fang ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Bone Marrow ◽

Stromal Cell ◽

Bone Marrow Stromal Cell ◽

Oxygen Species ◽

Marrow Stromal Cell ◽

Stromal Cell Derived Factor ◽

Electrical Burns ◽

Targeted Release ◽

Cell Chemotaxis

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The Chemokine Receptor CXCR-4 Is Expressed on CD34+Hematopoietic Progenitors and Leukemic Cells and Mediates Transendothelial Migration Induced by Stromal Cell-Derived Factor-1

Blood ◽

10.1182/blood.v91.12.4523.412k04_4523_4530 ◽

1998 ◽

Vol 91 (12) ◽

pp. 4523-4530 ◽

Cited By ~ 7

Author(s):

Robert Möhle ◽

Frank Bautz ◽

Shahin Rafii ◽

Malcolm A.S. Moore ◽

Wolfram Brugger ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Progenitor Cells ◽

Stromal Cell ◽

Leukemic Cell ◽

Transendothelial Migration ◽

Leukemic Cells ◽

Hematopoietic Progenitor ◽

Leukemic Cell Lines ◽

Stromal Cell Derived Factor

The chemokine stromal cell-derived factor-1 (SDF-1) and its receptor CXCR-4 (fusin, LESTR) are likely to be involved in the trafficking of hematopoietic progenitor and stem cells, as suggested by the reduced bone marrow hematopoiesis in SDF-1–deficient mice and the chemotactic effect of SDF-1 on CD34+ progenitor cells. Migration of leukemic cells might also depend on the expression of chemokine receptors. Therefore, we analyzed expression of CXCR-4 on mobilized normal CD34+ progenitors and leukemic cells. In addition, SDF-1–induced transendothelial migration across a bone marrow endothelial cell layer was assessed in vitro. By flow cytometry, CXCR-4 was found to be expressed in significant amounts on circulating CD34+ hematopoietic progenitor cells, including more primitive subsets (CD34+/CD38− and CD34+/Thy-1+ cells). In accordance with the immunofluorescence data, CD34+ progenitors efficiently migrated across endothelium in response to SDF-1 containing conditioned medium from the stromal cell line MS-5. Leukemic blasts (mostly CD34+) from patients with acute myeloblastic leukemia (AML) expressed variable amounts of CXCR-4, which was functionally active, as demonstrated by a positive correlation between the SDF-1–induced transendothelial migration and the cell surface density of CXCR-4 (r = 0.97). Also recombinant SDF-1β induced migration of CXCR-4–positive leukemic blasts. The effect of both conditioned medium and recombinant SDF-1 was inhibited by a CXCR-4 blocking antibody. In contrast, CD34+ leukemic cell lines (KG1, KG1a, Kasumi-1, MOLM-1) expressed low levels or were negative for CXCR-4, and did not migrate. By reverse transcriptase-polymerase chain reaction (RT-PCR), however, basal levels of CXCR-4 mRNA were also detected in all leukemic cell lines. We conclude that CXCR-4 is expressed on CD34+cells including more primitive, pluripotent progenitors, and may therefore play a role in the homing of hematopoietic stem cells. CXCR-4 expressed in variable amounts on primary AML leukemic cells is functionally active and may be involved in the trafficking of malignant hematopoietic cells.

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