Cleaved forms of soluble urokinase receptor (c-suPAR) have been detected in body fluids from patients affected by various tumors. We recently reported increased c-suPAR levels in sera of healthy donors during granulocyte colony-stimulating factor (G-CSF)-induced mobilization of CD34+ hematopoietic stem cells (HSC). In vitro, c-suPAR or its derived chemotactic peptide (uPAR84-95) stimulated migration of human CD34+ HSCs and inactivated CXCR4, the chemokine receptor primarily responsible for HSC retention in bone marrow. These results suggested that c-suPAR could potentially contribute to regulate HSC trafficking from and to bone marrow. Therefore, we investigated uPAR84-95 effects on mobilization of mouse CD34+ hematopoietic stem/progenitor cells (HSC/HPC). We first showed that uPAR84-95 stimulated in vitro dose-dependent migration of mouse CD34+ M1 leukemia cells and inactivated murine CXCR4. uPAR 84-95 capability to induce mouse HSC/HPC release from bone marrow and migration into the circulation was then investigated in vivo. uPAR 84-95 i.p. administration induced rapid leukocytosis, which was associated with an increase in peripheral blood CD34+ HSCs/HPCs. In vitro colony assays confirmed that uPAR84-95 mobilized hematopoietic progenitors, showing an absolute increase in circulating colony-forming cells. uPAR84-95 mobilizing activity was comparable to that of G-CSF; however, neither synergistic nor additive effect was observed in combining the two molecules. These findings show for the first time in vivo biological effects of c-suPAR. Its capability to mobilize HSCs suggests potential clinical applications in HSC transplantation.
ASJC Scopus subject areas
- Cancer Research