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Department of Internal Medicine V, University of Heidelberg, Germany
Correspondence: Dr. S. Fruehauf, Department of Internal Medicine V, University of Heidelberg, Hospitalstrasse 3, D-69115, Heidelberg, Germany. E-mail: stefan_fruehauf{at}med.uni-heidelberg.de
Hematopoietic cells extend multiple podia of yet unknown function. Our
morphological studies using scanning electron microscopy and functional
studies using time-lapse video microscopy suggest that podia formed by
CD34+ hematopoietic stem cells (HSC) on the bone marrow stroma
component fibronectin are characteristic of lamellipodia at the leading
edge and uropodia at the trailing edge, cytoskeletal structures that
have previously been shown to be responsible for cell locomotion of
lymphocytes. In the leukemic cells studied here, stroma-derived
factor-1
(SDF-1) led to a significant eightfold increase in
transmigration (BCR-ABL-positive BV173 leukemia cell line;
P<0.05) and podia formation in all BCR-ABL-positive
leukemic cell lines studied (BV173, K562, 32Dp210) and in two of three
BCR-ABL-negative lines (HL60, 32D, not KG1a). We could show that
SDF-1 exposure led to a down-regulation of the gene expression of
the chemokine receptors CCR4, CXCR4, and CXCR5, which are associated
with cell motility and podia formation, indicating a negative feedback
control. In BCR-ABL-positive leukemic cells, the effects of SDF-1 on
podia formation and cell migration were independent of BCR-ABL-tyrosine
kinase activity. Our data are compatible with the hypothesis that
formation of specific podia by hematopoietic cells is associated with
egression of these cells from the bone marrow.
Key Words: SDF-1 • transmigration • leukemia • BCR-ABL
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