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Blood, 15 March 2002, Vol. 99, No. 6, pp. 2023-2031
HEMATOPOIESIS
Increased binding and defective migration across fibronectin of
cycling hematopoietic progenitor cells
Olivier Giet,
Dirk R. Van Bockstaele,
Ivano Di
Stefano,
Sandra Huygen,
Roland Greimers,
Yves Beguin, and
André Gothot
From the Departments of Medicine/Hematology, Laboratory
Medicine, and Pathology, University of Liège, Belgium; and
Laboratory of Experimental Hematology, University of Antwerp, Belgium.
Engraftment of hematopoietic progenitor cells has been shown to
decrease during cell cycle transit. We studied cell cycle-associated changes in adhesion and migration of mitotically activated cord blood
CD34+ cells. Migration toward medium conditioned by the
stromal-derived factor-1-producing cell line MS-5 was studied in
bovine serum albumin- and fibronectin (Fn)-coated transwells.
Migration was reduced in cycling CD34+ cells and long-term
culture-initiating cells (LTC-ICs) compared with their noncycling
counterparts across Fn but not across bovine serum albumin. Conversely,
Fn binding was higher in cycling CD34+ cells and LTC-ICs
compared with noncycling progenitor cells, while adhesion of both
subsets to bovine serum albumin was undetectable. The contribution of
 4 and 5 integrins in mediating adhesion and migration of
activated CD34+ cells onto Fn was analyzed by
neutralization experiments. While 4-mediated Fn binding decreased
during G2/M, 5 integrin-mediated adhesion increased
during transit from G0/G1 to S and
G2/M phases. As for migration, the contribution of 4
integrin was similar in all phases, whereas 5-directed migration was
lower in G2/M compared with G0/G1
and S phases. Defective migration of cycling CD34+ cells
was not due to differences in 5 integrin expression. In conclusion,
chemotaxis across Fn is less efficient in cycling progenitor cells in
correlation with an increased Fn binding capacity. In addition, 4
and 5 integrin functions are independently modulated during cell
cycle transit.
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