Abstract
Abstract Cleaved forms of soluble urokinase-receptor (c-suPAR) have been detected in body fluids from patients affected by various tumors. We reported increased c-suPAR levels in sera of healthy donors during granulocyte colony-stimulating factor (G-CSF)-induced mobilization of CD34+hematopoietic stem cells (HSCs). Then, we investigated the effects of uPAR84–95, a c-suPAR-derived chemotactic peptide, on mobilization of mouse CD34+ hematopoietic stem/progenitor cells (HSCs/HPCs). We first demonstrated that uPAR84–95 stimulated in vitro dose-dependent migration of mouse CD34+ M1 leukemia cells and inactivated CXCR4, the chemokine receptor primarily responsible for HSC retention in bone marrow (BM). uPAR84–95 intraperitoneal 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 combining the two molecules. These findings demonstrate for the first time in vivo biological effects of c-suPAR. Its capability to mobilize HSCs suggests potential clinical applications in HSC transplantation.
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