MIM regulates the trafficking of bone marrow cells via modulating surface expression of CXCR4

T. Zhan, C. Cao, L. Li, N. Gu, C. I. Civin, X. Zhan

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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 .

Original languageEnglish (US)
Pages (from-to)1327-1334
Number of pages8
Issue number6
StatePublished - Jun 1 2016
Externally publishedYes

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine


Dive into the research topics of 'MIM regulates the trafficking of bone marrow cells via modulating surface expression of CXCR4'. Together they form a unique fingerprint.

Cite this