BCR/ABL Expression of Myeloid Progenitors Increases beta sub(1)-Integrin Mediated Adhesion to Stromal Cells
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 marr...
Gespeichert in:
Veröffentlicht in: | Journal of molecular biology 2008-04, Vol.377 (4), p.1082-1093 |
---|---|
Hauptverfasser: | , , , , , , |
Format: | Artikel |
Sprache: | eng |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 1093 |
---|---|
container_issue | 4 |
container_start_page | 1082 |
container_title | Journal of molecular biology |
container_volume | 377 |
creator | Fierro, F A Taubenberger, A Puech, PH Ehninger, G Bornhauser, M Muller, D J Illmer, T |
description | 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 beta sub(1)-integrin has a major role in mediating the adhesion of leukemic cells to BMSC. Indeed, the beta sub(1)-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 beta sub(1)-integrin expression, no significant difference of beta sub(1)-integrin mRNA levels could be detected, indicating a post-transcriptional regulation of beta sub(1)-comprising integrin heterodimers by BCR/ABL. The data presented here argue that the interaction of beta sub(1)-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. |
doi_str_mv | 10.1016/j.jmb.2008.01.085 |
format | Article |
fullrecord | <record><control><sourceid>proquest</sourceid><recordid>TN_cdi_proquest_miscellaneous_20851325</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>20851325</sourcerecordid><originalsourceid>FETCH-proquest_miscellaneous_208513253</originalsourceid><addsrcrecordid>eNqNjstOwzAQAH0AifL4AG57QnCIu3ZIlWsbFVGJSgi4V06zLQ6Ot3gdCf6eCvEBnOYyGo1S1wa1QTOb9rofWm0Ra41GY12dqAmitYWty9mZOhfpEbEq7-uJ-lg0L9P54gmWX4dEIp4j8A7W3xTYd_CceE_RZ04Cq7hN5IQEWsoOZGxvzV2xipn2yUdYU-ddpg7m3Tv9djLDa048uAANhSCX6nTngtDVHy_UzcPyrXksDok_R5K8Gbxsj6aLxKNs7HHdlLYq_y3-ADYnT9Y</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>20851325</pqid></control><display><type>article</type><title>BCR/ABL Expression of Myeloid Progenitors Increases beta sub(1)-Integrin Mediated Adhesion to Stromal Cells</title><source>Access via ScienceDirect (Elsevier)</source><creator>Fierro, F A ; Taubenberger, A ; Puech, PH ; Ehninger, G ; Bornhauser, M ; Muller, D J ; Illmer, T</creator><creatorcontrib>Fierro, F A ; Taubenberger, A ; Puech, PH ; Ehninger, G ; Bornhauser, M ; Muller, D J ; Illmer, T</creatorcontrib><description>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 beta sub(1)-integrin has a major role in mediating the adhesion of leukemic cells to BMSC. Indeed, the beta sub(1)-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 beta sub(1)-integrin expression, no significant difference of beta sub(1)-integrin mRNA levels could be detected, indicating a post-transcriptional regulation of beta sub(1)-comprising integrin heterodimers by BCR/ABL. The data presented here argue that the interaction of beta sub(1)-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.</description><identifier>ISSN: 0022-2836</identifier><identifier>DOI: 10.1016/j.jmb.2008.01.085</identifier><language>eng</language><ispartof>Journal of molecular biology, 2008-04, Vol.377 (4), p.1082-1093</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Fierro, F A</creatorcontrib><creatorcontrib>Taubenberger, A</creatorcontrib><creatorcontrib>Puech, PH</creatorcontrib><creatorcontrib>Ehninger, G</creatorcontrib><creatorcontrib>Bornhauser, M</creatorcontrib><creatorcontrib>Muller, D J</creatorcontrib><creatorcontrib>Illmer, T</creatorcontrib><title>BCR/ABL Expression of Myeloid Progenitors Increases beta sub(1)-Integrin Mediated Adhesion to Stromal Cells</title><title>Journal of molecular biology</title><description>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 beta sub(1)-integrin has a major role in mediating the adhesion of leukemic cells to BMSC. Indeed, the beta sub(1)-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 beta sub(1)-integrin expression, no significant difference of beta sub(1)-integrin mRNA levels could be detected, indicating a post-transcriptional regulation of beta sub(1)-comprising integrin heterodimers by BCR/ABL. The data presented here argue that the interaction of beta sub(1)-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.</description><issn>0022-2836</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNqNjstOwzAQAH0AifL4AG57QnCIu3ZIlWsbFVGJSgi4V06zLQ6Ot3gdCf6eCvEBnOYyGo1S1wa1QTOb9rofWm0Ra41GY12dqAmitYWty9mZOhfpEbEq7-uJ-lg0L9P54gmWX4dEIp4j8A7W3xTYd_CceE_RZ04Cq7hN5IQEWsoOZGxvzV2xipn2yUdYU-ddpg7m3Tv9djLDa048uAANhSCX6nTngtDVHy_UzcPyrXksDok_R5K8Gbxsj6aLxKNs7HHdlLYq_y3-ADYnT9Y</recordid><startdate>20080404</startdate><enddate>20080404</enddate><creator>Fierro, F A</creator><creator>Taubenberger, A</creator><creator>Puech, PH</creator><creator>Ehninger, G</creator><creator>Bornhauser, M</creator><creator>Muller, D J</creator><creator>Illmer, T</creator><scope>7T5</scope><scope>7TM</scope><scope>H94</scope></search><sort><creationdate>20080404</creationdate><title>BCR/ABL Expression of Myeloid Progenitors Increases beta sub(1)-Integrin Mediated Adhesion to Stromal Cells</title><author>Fierro, F A ; Taubenberger, A ; Puech, PH ; Ehninger, G ; Bornhauser, M ; Muller, D J ; Illmer, T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-proquest_miscellaneous_208513253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fierro, F A</creatorcontrib><creatorcontrib>Taubenberger, A</creatorcontrib><creatorcontrib>Puech, PH</creatorcontrib><creatorcontrib>Ehninger, G</creatorcontrib><creatorcontrib>Bornhauser, M</creatorcontrib><creatorcontrib>Muller, D J</creatorcontrib><creatorcontrib>Illmer, T</creatorcontrib><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Journal of molecular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fierro, F A</au><au>Taubenberger, A</au><au>Puech, PH</au><au>Ehninger, G</au><au>Bornhauser, M</au><au>Muller, D J</au><au>Illmer, T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>BCR/ABL Expression of Myeloid Progenitors Increases beta sub(1)-Integrin Mediated Adhesion to Stromal Cells</atitle><jtitle>Journal of molecular biology</jtitle><date>2008-04-04</date><risdate>2008</risdate><volume>377</volume><issue>4</issue><spage>1082</spage><epage>1093</epage><pages>1082-1093</pages><issn>0022-2836</issn><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 beta sub(1)-integrin has a major role in mediating the adhesion of leukemic cells to BMSC. Indeed, the beta sub(1)-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 beta sub(1)-integrin expression, no significant difference of beta sub(1)-integrin mRNA levels could be detected, indicating a post-transcriptional regulation of beta sub(1)-comprising integrin heterodimers by BCR/ABL. The data presented here argue that the interaction of beta sub(1)-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.</abstract><doi>10.1016/j.jmb.2008.01.085</doi></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0022-2836 |
ispartof | Journal of molecular biology, 2008-04, Vol.377 (4), p.1082-1093 |
issn | 0022-2836 |
language | eng |
recordid | cdi_proquest_miscellaneous_20851325 |
source | Access via ScienceDirect (Elsevier) |
title | BCR/ABL Expression of Myeloid Progenitors Increases beta sub(1)-Integrin Mediated Adhesion to Stromal Cells |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T18%3A22%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=BCR/ABL%20Expression%20of%20Myeloid%20Progenitors%20Increases%20beta%20sub(1)-Integrin%20Mediated%20Adhesion%20to%20Stromal%20Cells&rft.jtitle=Journal%20of%20molecular%20biology&rft.au=Fierro,%20F%20A&rft.date=2008-04-04&rft.volume=377&rft.issue=4&rft.spage=1082&rft.epage=1093&rft.pages=1082-1093&rft.issn=0022-2836&rft_id=info:doi/10.1016/j.jmb.2008.01.085&rft_dat=%3Cproquest%3E20851325%3C/proquest%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=20851325&rft_id=info:pmid/&rfr_iscdi=true |