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, Nunzia Montuori

Research output: Contribution to journalArticle

Abstract

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 α6 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.

Original languageEnglish
Pages (from-to)2476-2484
Number of pages9
JournalBlood
Volume108
Issue number7
DOIs
Publication statusPublished - Oct 1 2006

ASJC Scopus subject areas

  • Hematology

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    Selleri, C., Ragno, P., Ricci, P., Visconte, V., Scarpato, N., Carriero, M. V., Rotoli, B., Rossi, G., & Montuori, N. (2006). The metastasis-associated 67-kDa laminin receptor is involved in G-CSF-induced hematopoietic stem cell mobilization. Blood, 108(7), 2476-2484. https://doi.org/10.1182/blood-2005-11-012625