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The major function of bone marrow is growth stimulation and differentiation of hematopoietic stem cells (Dorshkind, 1990). In vitro studies of long-term bone-marrow cultures (LTBMC) have emphasized the essential role of bone-marrow stromal cells in hematopoiesis (Dorshkind, 1990). Colonization of bone-marrow precursor cells is mediated by contacts between adhesion receptors on bone-marrow stromal cells and on precursor hematopoietic cells (Leavesley et al., 1994). These precursor cells interact directly with stromal cells, but also indirectly via the extracellular matrix (ECM) proteins. As a result of this type of interaction, intracellular signalling of stromal cells can take place followed by activation and production of growth factors or cytokines. Growth factors and cytokines are essential for the regulation of cell growth and differentiation (Dorshkind, 1990). Different adhesion pathways have been described for the leukocyte-endothelial-cell interaction pathways (Elices et al., 1990). In particular, the role of integrins in cell contacts as well as in the linkage of ECM proteins with the intracellular signal transduction pathways seems to be essential in basic development of the hematopoiesis, but may also be significant in aberrant processes such as tumor-cell invasion (Juliano, 1994;Clark and Brugge, 1995). So far, for the leukemic-cell/bone-marrow stromal-cell interaction, integrins appear to be essential, but the details of this interaction remain largely unknown.The aim of this study was to investigate the variations in adhesion and migratory behavior of leukemic cells on human bone-marrow stromal cells. Therefore, we developed an in vitro model to study the basic interaction patterns of leukemic cells with human bone-marrow stromal cells. Adhesion, spreading and migration of erythroleukemic HEL92.1.7 and K562 cells together with the promyeloid HL60 cells on human BM stromal cells was monitored at the ultrastructural level and with phase-contrast microscopy. The role of adhesion molecules was studied, especially that of the pl-integrins. Discrete distribution of cell-surface molecules on these human leukemic cell lines and BM stromal cells was associated with a clear variation in adhesion and migration patterns. Adhesion and migration blocking studies using MAbs against the various adhesion molecules proved that the P1-integrins VLA-4 and VLA-5 in particular fulfil an essential function in tumor-cell adhesion and migration. MATERIAL AND METHODS Cells and culture conditionsBone-marrow stromal cells. Bone-marrow aspirates were obtained from donors without hematologic abnormalities, after informed consent. The aspirates were obtained from the sternum during coronary bypass operations and were diluted with an equal volume of RPMI 1640 containing heparin. A buf€y coat was isolated by centrifugation for 15 min at 2,000 rpm. Erythrocytes were lysed with NbCl(8.3 g/1 containing 1 g NaHC03 and 37 mg EDTA) buffer and washed 3 times with RPMI-1640 medium. The remaining cells were collected and cultured. A human b...

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