Bcr/Abl expression stimulates integrin function in hematopoietic cell lines

Gianfranco Bazzoni, Nadia Carlesso, James D. Griffin, Martin E. Hemler

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)521-528
Number of pages8
JournalJournal of Clinical Investigation
Volume98
Issue number2
StatePublished - Jul 15 1996
Externally publishedYes

Fingerprint

Integrin alpha5beta1
Integrins
Cell Line
bcr-abl Fusion Proteins
Cell Adhesion
Integrin alpha4beta1
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Fibronectins
abl Genes
Ligands
Vascular Cell Adhesion Molecule-1
Interleukin-3
Granulocyte-Macrophage Colony-Stimulating Factor
Extracellular Matrix
Phosphotransferases
Temperature

Keywords

  • Bcr/Abl
  • cell adhesion
  • chronic myelogenous leukemia
  • fibronectin
  • integrin

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Bcr/Abl expression stimulates integrin function in hematopoietic cell lines. / Bazzoni, Gianfranco; Carlesso, Nadia; Griffin, James D.; Hemler, Martin E.

In: Journal of Clinical Investigation, Vol. 98, No. 2, 15.07.1996, p. 521-528.

Research output: Contribution to journalArticle

Bazzoni, Gianfranco ; Carlesso, Nadia ; Griffin, James D. ; Hemler, Martin E. / Bcr/Abl expression stimulates integrin function in hematopoietic cell lines. In: Journal of Clinical Investigation. 1996 ; Vol. 98, No. 2. pp. 521-528.
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