BCR/ABL Expression of Myeloid Progenitors Increases β1-Integrin Mediated Adhesion to Stromal Cells

Fernando A Fierro, Anna Taubenberger, Pierre Henri Puech, Gerhard Ehninger, Martin Bornhauser, Daniel J. Muller, Thomas Illmer

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

The expression of the fusion protein BCR/ABL is a hallmark of chronic myeloid leukemia. BCR/ABL is a constitutively active tyrosine kinase influencing cell proliferation, apoptosis, and differentiation. To what extent and by which mechanism BCR/ABL affects the adhesion of leukemic cells to bone marrow stromal cells (BMSC) is controversial. To characterize adhesion of BCR/ABL-transformed 32D cells (32D-BCR/ABL) to the BMSC line M2-10B4, we used washing assays and single-cell force spectroscopy (SCFS). Compared to control 32D cells (32D-V), 32D-BCR/ABL developed threefold higher adhesion forces. This enhanced cell adhesion could be reduced to control levels after specifically inhibiting the activity of the tyrosine kinase BCR/ABL using imatinib mesylate (IM). SCFS showed that the adhesion forces of 32D-BCR/ABL were strongest to fibronectin and collagen type I, suggesting that β1-integrin has a major role in mediating the adhesion of leukemic cells to BMSC. Indeed, the β1-integrin blocking antibody Ha2/5 abrogated the attachment of 32D-V and 32D-BCR/ABL cells to BMSC. Although 32D-BCR/ABL cells show significantly increased β1-integrin expression, no significant difference of β1-integrin mRNA levels could be detected, indicating a post-transcriptional regulation of β1-comprising integrin heterodimers by BCR/ABL. The data presented here argue that the interaction of β1-integrin and extracellular matrix components is functionally important in leukemic cells expressing high-levels of BCR/ABL, and could provide a rationale for the development of optimized targeted therapies.

Original languageEnglish (US)
Pages (from-to)1082-1093
Number of pages12
JournalJournal of Molecular Biology
Volume377
Issue number4
DOIs
StatePublished - Apr 4 2008
Externally publishedYes

Fingerprint

Stromal Cells
Integrins
Mesenchymal Stromal Cells
Cell Adhesion
Protein-Tyrosine Kinases
Spectrum Analysis
Blocking Antibodies
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Collagen Type I
Fibronectins
Extracellular Matrix
Cell Differentiation
Cell Proliferation
Apoptosis
Cell Line
Messenger RNA
Proteins

Keywords

  • atomic force microscopy
  • BCR/ABL
  • bone marrow stromal cells
  • cell adhesion
  • chronic myeloid leukemia

ASJC Scopus subject areas

  • Virology

Cite this

Fierro, F. A., Taubenberger, A., Puech, P. H., Ehninger, G., Bornhauser, M., Muller, D. J., & Illmer, T. (2008). BCR/ABL Expression of Myeloid Progenitors Increases β1-Integrin Mediated Adhesion to Stromal Cells. Journal of Molecular Biology, 377(4), 1082-1093. https://doi.org/10.1016/j.jmb.2008.01.085

BCR/ABL Expression of Myeloid Progenitors Increases β1-Integrin Mediated Adhesion to Stromal Cells. / Fierro, Fernando A; Taubenberger, Anna; Puech, Pierre Henri; Ehninger, Gerhard; Bornhauser, Martin; Muller, Daniel J.; Illmer, Thomas.

In: Journal of Molecular Biology, Vol. 377, No. 4, 04.04.2008, p. 1082-1093.

Research output: Contribution to journalArticle

Fierro, FA, Taubenberger, A, Puech, PH, Ehninger, G, Bornhauser, M, Muller, DJ & Illmer, T 2008, 'BCR/ABL Expression of Myeloid Progenitors Increases β1-Integrin Mediated Adhesion to Stromal Cells', Journal of Molecular Biology, vol. 377, no. 4, pp. 1082-1093. https://doi.org/10.1016/j.jmb.2008.01.085
Fierro, Fernando A ; Taubenberger, Anna ; Puech, Pierre Henri ; Ehninger, Gerhard ; Bornhauser, Martin ; Muller, Daniel J. ; Illmer, Thomas. / BCR/ABL Expression of Myeloid Progenitors Increases β1-Integrin Mediated Adhesion to Stromal Cells. In: Journal of Molecular Biology. 2008 ; Vol. 377, No. 4. pp. 1082-1093.
@article{a92a8df8e66c4f50972fa169eac16451,
title = "BCR/ABL Expression of Myeloid Progenitors Increases β1-Integrin Mediated Adhesion to Stromal Cells",
abstract = "The expression of the fusion protein BCR/ABL is a hallmark of chronic myeloid leukemia. BCR/ABL is a constitutively active tyrosine kinase influencing cell proliferation, apoptosis, and differentiation. To what extent and by which mechanism BCR/ABL affects the adhesion of leukemic cells to bone marrow stromal cells (BMSC) is controversial. To characterize adhesion of BCR/ABL-transformed 32D cells (32D-BCR/ABL) to the BMSC line M2-10B4, we used washing assays and single-cell force spectroscopy (SCFS). Compared to control 32D cells (32D-V), 32D-BCR/ABL developed threefold higher adhesion forces. This enhanced cell adhesion could be reduced to control levels after specifically inhibiting the activity of the tyrosine kinase BCR/ABL using imatinib mesylate (IM). SCFS showed that the adhesion forces of 32D-BCR/ABL were strongest to fibronectin and collagen type I, suggesting that β1-integrin has a major role in mediating the adhesion of leukemic cells to BMSC. Indeed, the β1-integrin blocking antibody Ha2/5 abrogated the attachment of 32D-V and 32D-BCR/ABL cells to BMSC. Although 32D-BCR/ABL cells show significantly increased β1-integrin expression, no significant difference of β1-integrin mRNA levels could be detected, indicating a post-transcriptional regulation of β1-comprising integrin heterodimers by BCR/ABL. The data presented here argue that the interaction of β1-integrin and extracellular matrix components is functionally important in leukemic cells expressing high-levels of BCR/ABL, and could provide a rationale for the development of optimized targeted therapies.",
keywords = "atomic force microscopy, BCR/ABL, bone marrow stromal cells, cell adhesion, chronic myeloid leukemia",
author = "Fierro, {Fernando A} and Anna Taubenberger and Puech, {Pierre Henri} and Gerhard Ehninger and Martin Bornhauser and Muller, {Daniel J.} and Thomas Illmer",
year = "2008",
month = "4",
day = "4",
doi = "10.1016/j.jmb.2008.01.085",
language = "English (US)",
volume = "377",
pages = "1082--1093",
journal = "Journal of Molecular Biology",
issn = "0022-2836",
publisher = "Academic Press Inc.",
number = "4",

}

TY - JOUR

T1 - BCR/ABL Expression of Myeloid Progenitors Increases β1-Integrin Mediated Adhesion to Stromal Cells

AU - Fierro, Fernando A

AU - Taubenberger, Anna

AU - Puech, Pierre Henri

AU - Ehninger, Gerhard

AU - Bornhauser, Martin

AU - Muller, Daniel J.

AU - Illmer, Thomas

PY - 2008/4/4

Y1 - 2008/4/4

N2 - The expression of the fusion protein BCR/ABL is a hallmark of chronic myeloid leukemia. BCR/ABL is a constitutively active tyrosine kinase influencing cell proliferation, apoptosis, and differentiation. To what extent and by which mechanism BCR/ABL affects the adhesion of leukemic cells to bone marrow stromal cells (BMSC) is controversial. To characterize adhesion of BCR/ABL-transformed 32D cells (32D-BCR/ABL) to the BMSC line M2-10B4, we used washing assays and single-cell force spectroscopy (SCFS). Compared to control 32D cells (32D-V), 32D-BCR/ABL developed threefold higher adhesion forces. This enhanced cell adhesion could be reduced to control levels after specifically inhibiting the activity of the tyrosine kinase BCR/ABL using imatinib mesylate (IM). SCFS showed that the adhesion forces of 32D-BCR/ABL were strongest to fibronectin and collagen type I, suggesting that β1-integrin has a major role in mediating the adhesion of leukemic cells to BMSC. Indeed, the β1-integrin blocking antibody Ha2/5 abrogated the attachment of 32D-V and 32D-BCR/ABL cells to BMSC. Although 32D-BCR/ABL cells show significantly increased β1-integrin expression, no significant difference of β1-integrin mRNA levels could be detected, indicating a post-transcriptional regulation of β1-comprising integrin heterodimers by BCR/ABL. The data presented here argue that the interaction of β1-integrin and extracellular matrix components is functionally important in leukemic cells expressing high-levels of BCR/ABL, and could provide a rationale for the development of optimized targeted therapies.

AB - The expression of the fusion protein BCR/ABL is a hallmark of chronic myeloid leukemia. BCR/ABL is a constitutively active tyrosine kinase influencing cell proliferation, apoptosis, and differentiation. To what extent and by which mechanism BCR/ABL affects the adhesion of leukemic cells to bone marrow stromal cells (BMSC) is controversial. To characterize adhesion of BCR/ABL-transformed 32D cells (32D-BCR/ABL) to the BMSC line M2-10B4, we used washing assays and single-cell force spectroscopy (SCFS). Compared to control 32D cells (32D-V), 32D-BCR/ABL developed threefold higher adhesion forces. This enhanced cell adhesion could be reduced to control levels after specifically inhibiting the activity of the tyrosine kinase BCR/ABL using imatinib mesylate (IM). SCFS showed that the adhesion forces of 32D-BCR/ABL were strongest to fibronectin and collagen type I, suggesting that β1-integrin has a major role in mediating the adhesion of leukemic cells to BMSC. Indeed, the β1-integrin blocking antibody Ha2/5 abrogated the attachment of 32D-V and 32D-BCR/ABL cells to BMSC. Although 32D-BCR/ABL cells show significantly increased β1-integrin expression, no significant difference of β1-integrin mRNA levels could be detected, indicating a post-transcriptional regulation of β1-comprising integrin heterodimers by BCR/ABL. The data presented here argue that the interaction of β1-integrin and extracellular matrix components is functionally important in leukemic cells expressing high-levels of BCR/ABL, and could provide a rationale for the development of optimized targeted therapies.

KW - atomic force microscopy

KW - BCR/ABL

KW - bone marrow stromal cells

KW - cell adhesion

KW - chronic myeloid leukemia

UR - http://www.scopus.com/inward/record.url?scp=40849120282&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=40849120282&partnerID=8YFLogxK

U2 - 10.1016/j.jmb.2008.01.085

DO - 10.1016/j.jmb.2008.01.085

M3 - Article

C2 - 18313694

AN - SCOPUS:40849120282

VL - 377

SP - 1082

EP - 1093

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 4

ER -