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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.
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Submitted November 17, 2005
Accepted May 26, 2006
The metastasis-associated 67 kDa laminin receptor is
involved in G-CSF-induced hematopoietic stem cell
mobilization
Carmine Selleri, Pia Ragno, Patrizia Ricci, Valeria Visconte, Nicola Scarpato, Maria Vincenza Carriero, Bruno Rotoli, Guido Rossi, and Nunzia Montuori*
Department of Biochemistry and Medical Biotechnology, 'Federico II' University, Naples, Italy
Institute of Experimental Endocrinology and Oncology, National Research Council, Naples, Italy
Department of Cellular and Molecular Biology and Pathology, 'Federico II' University, Naples
Department of Experimental Oncology, National Cancer Institute, Naples, Italy
* Corresponding author; email: nmontuor{at}unina.it.
The 67 kDa laminin receptor (67LR) is a non-integrin
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, the level of 67LR
expression in G-CSF-mobilized HSCs significantly
correlated with mobilization efficiency. During G-CSF-
induced HSC mobilization, the expression of laminin
receptors switched from  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
upregulation 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.
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