Bcr/Abl expression stimulates integrin function in hematopoietic cell lines.
Cell adhesion to the extracellular matrix is largely mediated by adhesion molecules of the integrin family and is often diminished upon oncogenic transformation. However, we show here that the chronic myelogenous leukemia oncogene Bcr/Abl has positive effects on VLA-4 and VLA-5 integrin function. The presence of Bcr/Abl in the GM-CSF- or IL-3-dependent hematopoietic cell lines MO7e, 32D, and BaF/3 enhanced cell binding to both soluble and immobilized fibronectin. The effect was due to enhanced function of the VLA-5 integrin fibronectin receptor and not to increased surface expression. In parallel, Bcr/Abl stimulated cell adhesion to the VLA-4 integrin ligand VCAM-1. Stimulation of VLA-5 function directly correlated with induction of Bcr/Abl tyrosine kinase activity in a temperature-sensitive kinase mutant. Thus, Bcr/Abl stimulates integrin-dependent cell adhesion, by a mechanism involving increased ligand binding, with the tyrosine kinase activity of Bcr/Abl likely playing a key role. Consistent with these results, hematopoietic precursor cells from chronic myelogenous leukemia patients also showed increased adhesion to fibronectin.
Bazzoni
G
G
Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Carlesso
N
N
Griffin
J D
JD
Hemler
M E
ME
D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D005353:Fibronectins; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis* / Q000502:physiology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D039041:Integrin alpha4beta1; D016023:Integrins / Q000502:physiology*; D007377:Interleukin-3 / Q000494:pharmacology; D007700:Kinetics; D007942:Leukemia, Experimental; D007947:Leukemia, Megakaryoblastic, Acute; D051379:Mice; D017469:Receptors, Fibronectin / Q000502:physiology; D016201:Receptors, Lymphocyte Homing / Q000502:physiology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
D005353:Fibronectins; D039041:Integrin alpha4beta1; D016023:Integrins; D007377:Interleukin-3; D017469:Receptors, Fibronectin; D016201:Receptors, Lymphocyte Homing; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D016044:Fusion Proteins, bcr-abl