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Blood, 1 October 2006, Vol. 108, No. 7, pp. 2476-2484. Prepublished online as a Blood First Edition Paper on June 20, 2006; DOI 10.1182/blood-2005-11-012625.
TRANSPLANTATION The metastasis-associated 67-kDa laminin receptor is involved in G-CSF–induced hematopoietic stem cell mobilizationFrom the Department of Biochemistry and Medical Biotechnology, Institute of Experimental Endocrinology and Oncology (National Research Council), and Department of Cellular and Molecular Biology and Pathology, Federico II University, Naples; and Department of Experimental Oncology, National Cancer Institute, Naples, Italy.
The 67-kDa laminin receptor (67LR) is a nonintegrin cell-surface receptor with high affinity for laminin, which plays a key role in tumor invasion and metastasis. We investigated the role of 67LR in granulocyte colony-stimulating factor (G-CSF)–induced mobilization of CD34+ hematopoietic stem cells (HSCs) from 35 healthy donors. G-CSF–mobilized HSCs, including CD34+/CD38– cells, showed increased 67LR expression as compared with unstimulated marrow HSCs; noteworthy, also, is the fact that the level of 67LR expression in G-CSF–mobilized HSCs correlated significantly with mobilization efficiency. During G-CSF–induced HSC mobilization, the expression of laminin receptors switched from
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| Copyright © 2006 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
6 integrins, which mediated laminin-dependent adhesion of steady-state human marrow HSCs, to 67LR, responsible for G-CSF–mobilized HSC adhesion and migration toward laminin. In vitro G-CSF treatment, alone or combined with exposure to marrow-derived endothelial cells, induced 67LR up-regulation in marrow HSCs; moreover, anti-67LR antibodies significantly inhibited transendothelial migration of G-CSF–stimulated marrow HSCs. Finally, G-CSF–induced mobilization in mice was associated with 67LR up-regulation both in circulating and marrow CD34+ cells, and anti-67LR antibodies significantly reduced HSC mobilization, providing the first in vivo evidence for 67LR involvement in stem-cell egress from bone marrow after G-CSF administration. In conclusion, 67LR up-regulation in G-CSF–mobilized HSCs correlates with their successful mobilization and reflects its increase in marrow HSCs, which contributes to the egress from bone marrow by mediating laminin-dependent cell adhesion and transendothelial migration. 
