| First Author | Zhan T | Year | 2016 |
| Journal | Leukemia | Volume | 30 |
| Issue | 6 | Pages | 1327-34 |
| PubMed ID | 26965284 | Mgi Jnum | J:231913 |
| Mgi Id | MGI:5775495 | Doi | 10.1038/leu.2016.39 |
| Citation | Zhan T, et al. (2016) MIM regulates the trafficking of bone marrow cells via modulating surface expression of CXCR4. Leukemia 30(6):1327-34 |
| abstractText | 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. |
