title: MIM regulates the trafficking of bone marrow cells via modulating surface expression of CXCR4.
abstract: Missing in metastasis (MIM) is abundantly expressed in hematopoietic cells. Here we characterized the impact of MIM deficiency on murine bone marrow (BM) cells. Although MIM(-/-) cells proliferated similarly to wild type (WT), they exhibited stronger response to chemokine stromal-derived factor 1 (SDF-1), increase in surface expression of CXCR4, impaired CXCR4 internalization and constitutive activation of Rac, Cdc42 and p38. Transplantation of MIM(-/-) BM cells into lethally irradiated mice showed enhanced homing to BM, which was abolished when mice were pretreated with a p38 antagonist. Interestingly, MIM(-/-) BM cells, including hematopoietic stem and progenitor cells (HSPCs), showed two- to fivefold increase in mobilization into the peripheral blood upon treatment with AMD3100. In vitro, MIM(-/-) leukocytes were susceptible to AMD3100 and maintained increased response to AMD3100 for mobilization even after transfer into WT mice. MIM(-/-) mice had also a higher level of SDF-1 in the circulation. Our data highlighted an unprecedented role of MIM in the homeostasis of BM cells, including HSPCs, through modulation of the CXCR4/SDF-1 axis and interactions of BM leukocytes with their microenvironments.
authors.affiliation: Department of Pathology, Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: T
authors.initials: T
authors.lastname: Zhan
authors.affiliation: Department of Pathology, Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, USA.|Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: C
authors.initials: C
authors.lastname: Cao
authors.affiliation: Department of Pathology, Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, USA.|China Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing, China.
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.affiliation: China Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Sciences and Medical Engineering, Southeast University, Nanjing, China.
authors.forename: N
authors.initials: N
authors.lastname: Gu
authors.affiliation: Department of Pediatrics, Center for Stem Cell Biology and Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.|Departments of Pediatrics and Physiology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: C I
authors.initials: CI
authors.lastname: Civin
authors.affiliation: Department of Pathology, Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, USA.|Departments of Pediatrics and Physiology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.|Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: X
authors.initials: X
authors.lastname: Zhan
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D002465:Cell Movement; D054377:Chemokine CXCL12 / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006706:Homeostasis; D007962:Leukocytes; D051379:Mice; D008840:Microfilament Proteins / Q000502:physiology*; D009363:Neoplasm Proteins / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000378:metabolism
chemical_list: C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D008840:Microfilament Proteins; C473219:Mtss1 protein, mouse; D009363:Neoplasm Proteins; D019718:Receptors, CXCR4