Human acute myeloid leukemia cells bind to bone marrow stroma via a combination of β-1 and β-2 integrin mechanisms

Abstract

Acute myeloid leukemia (AML) cells respond to exogenous stimulation from myeloid growth factors that may be secreted by cells of the bone marrow (BM) stroma and retained by glycosaminoglycans in the extracellular matrix. We have analyzed the capacity of malignant cells from patients with AML to maintain close proximity to sites of growth factor production and retention by binding to BM stromal elements, including fibroblasts and extracellular matrix proteins. Leukemic cells from all cases of AML adhered to BM fibroblast (BMF) monolayers (mean ± standard error [SE] percentage binding, 30.9% ± 2.5%; n = 23) and to fibronectin and laminin (mean ± SE percentage binding, 28.0% ± 4.1%[n = 11] and 21.5% ± 2.3%[n = 8], respectively). Binding to bovine and human collagen type 1, vitronectin, hyaluronic acid, and albumin was minimal. Analysis of binding mechanisms indicated that very late antigen-4 (VLA-4) and VLA-5 were responsible for AML cell binding to fibronectin. Binding to laminin could be inhibited by antibody to the α chain of VLA-6. In contrast, AML cell adhesion to BMF monolayers was not impaired by blocking antibodies to either β1 or β2 integrins used alone, although the combination of anti-GD11/CD18 and anti-VLA-4 inhibited binding in more than 50% of cases. When anti-VLA-5 was added in these cases, mean ± SE inhibition of binding of 45.5% ± 9.1% (P < .001) was observed. Binding of AML cells to extracellular matrix proteins fibronectin and laminin is predominantly β1-integrin-dependent, but AML cell adhesion to BMF relies on the simultaneous involvement of β1 and β2 integrins as well as other currently unrecognized ligands. © 1993 by The American Society of Hematology.