Bacterial endotoxin enhances colorectal cancer cell adhesion and invasion through TLR-4 and NF-kappaB-dependent activation of the urokinase plasminogen activator system.

Hdl Handle:
http://hdl.handle.net/10147/201209
Title:
Bacterial endotoxin enhances colorectal cancer cell adhesion and invasion through TLR-4 and NF-kappaB-dependent activation of the urokinase plasminogen activator system.
Authors:
Killeen, S D; Wang, J H; Andrews, E J; Redmond, H P
Affiliation:
Department of Academic Surgery, Cork University Hospital and University College Cork, Cork, Ireland. sdfkilleen@eircom.net
Citation:
Bacterial endotoxin enhances colorectal cancer cell adhesion and invasion through TLR-4 and NF-kappaB-dependent activation of the urokinase plasminogen activator system. 2009, 100 (10):1589-602 Br. J. Cancer
Journal:
British journal of cancer
Issue Date:
19-May-2009
URI:
http://hdl.handle.net/10147/201209
DOI:
10.1038/sj.bjc.6604942
PubMed ID:
19436306
Additional Links:
http://www.nature.com/bjc/journal/v100/n10/pdf/6604942a.pdf; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696751/pdf/6604942a.pdf
Abstract:
Perioperative exposure to lipopolysaccharide (LPS) is associated with accelerated metastatic colorectal tumour growth. LPS directly affects cells through Toll-like receptor 4 (TLR-4) and the transcription factor NF-kappaB. The urokinase plasminogen activator (u-PA) system is intimately implicated in tumour cell extracellular matrix (ECM) interactions fundamental to tumour progression. Thus we sought to determine if LPS directly induces accelerated tumour cell ECM adhesion and invasion through activation of the u-PA system and to elucidate the cellular pathways involved. Human colorectal tumour cell lines were stimulated with LPS. u-PA concentration, u-PA activity, active u-PA, surface urokinase plasminogen activator receptor (u-PAR) and TLR-4 expression were assessed by ELISA, colorimetric assay, western blot analysis and flow cytometry respectively. In vitro tumour cell vitronectin adhesion and ECM invasion were analysed by vitronectin adhesion assay and ECM invasion chambers. u-PA and u-PAR function was inhibited with anti u-PA antibodies or the selective u-PA inhibitors amiloride or WXC-340, TLR-4 by TLR-4-blocking antibodies and NF-kappaB by the selective NF-kappaB inhibitor SN-50. LPS upregulates u-PA and u-PAR in a dose-dependent manner, enhancing in vitro tumour cell vitronectin adhesion and ECM invasion by >40% (P<0.01). These effects were ameliorated by u-PA and u-PAR inhibition. LPS activates NF-kappaB through TLR-4. TLR-4 and NF-kappaB inhibition ameliorated LPS-enhanced u-PA and u-PAR expression, tumour cell vitronectin adhesion and ECM invasion. LPS promotes tumour cell ECM adhesion and invasion through activation of the u-PA system in a TLR-4- and NF-kappaB-dependent manner.
Item Type:
Article
Language:
en
Description:
Perioperative exposure to lipopolysaccharide (LPS) is associated with accelerated metastatic colorectal tumour growth. LPS directly affects cells through Toll-like receptor 4 (TLR-4) and the transcription factor NF-kappaB. The urokinase plasminogen activator (u-PA) system is intimately implicated in tumour cell extracellular matrix (ECM) interactions fundamental to tumour progression. Thus we sought to determine if LPS directly induces accelerated tumour cell ECM adhesion and invasion through activation of the u-PA system and to elucidate the cellular pathways involved. Human colorectal tumour cell lines were stimulated with LPS. u-PA concentration, u-PA activity, active u-PA, surface urokinase plasminogen activator receptor (u-PAR) and TLR-4 expression were assessed by ELISA, colorimetric assay, western blot analysis and flow cytometry respectively. In vitro tumour cell vitronectin adhesion and ECM invasion were analysed by vitronectin adhesion assay and ECM invasion chambers. u-PA and u-PAR function was inhibited with anti u-PA antibodies or the selective u-PA inhibitors amiloride or WXC-340, TLR-4 by TLR-4-blocking antibodies and NF-kappaB by the selective NF-kappaB inhibitor SN-50. LPS upregulates u-PA and u-PAR in a dose-dependent manner, enhancing in vitro tumour cell vitronectin adhesion and ECM invasion by >40% (P<0.01). These effects were ameliorated by u-PA and u-PAR inhibition. LPS activates NF-kappaB through TLR-4. TLR-4 and NF-kappaB inhibition ameliorated LPS-enhanced u-PA and u-PAR expression, tumour cell vitronectin adhesion and ECM invasion. LPS promotes tumour cell ECM adhesion and invasion through activation of the u-PA system in a TLR-4- and NF-kappaB-dependent manner.
MeSH:
Amiloride; Antibodies; Bacterial Toxins; Caco-2 Cells; Carcinoma; Cell Adhesion; Cell Movement; Colorectal Neoplasms; Humans; Lipopolysaccharides; NF-kappa B; Neoplasm Invasiveness; Receptors, Urokinase Plasminogen Activator; Toll-Like Receptor 4; Tumor Cells, Cultured; Urokinase-Type Plasminogen Activator
ISSN:
1532-1827

Full metadata record

DC FieldValue Language
dc.contributor.authorKilleen, S Den
dc.contributor.authorWang, J Hen
dc.contributor.authorAndrews, E Jen
dc.contributor.authorRedmond, H Pen
dc.date.accessioned2012-01-10T11:41:00Z-
dc.date.available2012-01-10T11:41:00Z-
dc.date.issued2009-05-19-
dc.identifier.citationBacterial endotoxin enhances colorectal cancer cell adhesion and invasion through TLR-4 and NF-kappaB-dependent activation of the urokinase plasminogen activator system. 2009, 100 (10):1589-602 Br. J. Canceren
dc.identifier.issn1532-1827-
dc.identifier.pmid19436306-
dc.identifier.doi10.1038/sj.bjc.6604942-
dc.identifier.urihttp://hdl.handle.net/10147/201209-
dc.descriptionPerioperative exposure to lipopolysaccharide (LPS) is associated with accelerated metastatic colorectal tumour growth. LPS directly affects cells through Toll-like receptor 4 (TLR-4) and the transcription factor NF-kappaB. The urokinase plasminogen activator (u-PA) system is intimately implicated in tumour cell extracellular matrix (ECM) interactions fundamental to tumour progression. Thus we sought to determine if LPS directly induces accelerated tumour cell ECM adhesion and invasion through activation of the u-PA system and to elucidate the cellular pathways involved. Human colorectal tumour cell lines were stimulated with LPS. u-PA concentration, u-PA activity, active u-PA, surface urokinase plasminogen activator receptor (u-PAR) and TLR-4 expression were assessed by ELISA, colorimetric assay, western blot analysis and flow cytometry respectively. In vitro tumour cell vitronectin adhesion and ECM invasion were analysed by vitronectin adhesion assay and ECM invasion chambers. u-PA and u-PAR function was inhibited with anti u-PA antibodies or the selective u-PA inhibitors amiloride or WXC-340, TLR-4 by TLR-4-blocking antibodies and NF-kappaB by the selective NF-kappaB inhibitor SN-50. LPS upregulates u-PA and u-PAR in a dose-dependent manner, enhancing in vitro tumour cell vitronectin adhesion and ECM invasion by >40% (P<0.01). These effects were ameliorated by u-PA and u-PAR inhibition. LPS activates NF-kappaB through TLR-4. TLR-4 and NF-kappaB inhibition ameliorated LPS-enhanced u-PA and u-PAR expression, tumour cell vitronectin adhesion and ECM invasion. LPS promotes tumour cell ECM adhesion and invasion through activation of the u-PA system in a TLR-4- and NF-kappaB-dependent manner.en
dc.description.abstractPerioperative exposure to lipopolysaccharide (LPS) is associated with accelerated metastatic colorectal tumour growth. LPS directly affects cells through Toll-like receptor 4 (TLR-4) and the transcription factor NF-kappaB. The urokinase plasminogen activator (u-PA) system is intimately implicated in tumour cell extracellular matrix (ECM) interactions fundamental to tumour progression. Thus we sought to determine if LPS directly induces accelerated tumour cell ECM adhesion and invasion through activation of the u-PA system and to elucidate the cellular pathways involved. Human colorectal tumour cell lines were stimulated with LPS. u-PA concentration, u-PA activity, active u-PA, surface urokinase plasminogen activator receptor (u-PAR) and TLR-4 expression were assessed by ELISA, colorimetric assay, western blot analysis and flow cytometry respectively. In vitro tumour cell vitronectin adhesion and ECM invasion were analysed by vitronectin adhesion assay and ECM invasion chambers. u-PA and u-PAR function was inhibited with anti u-PA antibodies or the selective u-PA inhibitors amiloride or WXC-340, TLR-4 by TLR-4-blocking antibodies and NF-kappaB by the selective NF-kappaB inhibitor SN-50. LPS upregulates u-PA and u-PAR in a dose-dependent manner, enhancing in vitro tumour cell vitronectin adhesion and ECM invasion by >40% (P<0.01). These effects were ameliorated by u-PA and u-PAR inhibition. LPS activates NF-kappaB through TLR-4. TLR-4 and NF-kappaB inhibition ameliorated LPS-enhanced u-PA and u-PAR expression, tumour cell vitronectin adhesion and ECM invasion. LPS promotes tumour cell ECM adhesion and invasion through activation of the u-PA system in a TLR-4- and NF-kappaB-dependent manner.-
dc.language.isoenen
dc.relation.urlhttp://www.nature.com/bjc/journal/v100/n10/pdf/6604942a.pdfen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696751/pdf/6604942a.pdfen
dc.subject.meshAmiloride-
dc.subject.meshAntibodies-
dc.subject.meshBacterial Toxins-
dc.subject.meshCaco-2 Cells-
dc.subject.meshCarcinoma-
dc.subject.meshCell Adhesion-
dc.subject.meshCell Movement-
dc.subject.meshColorectal Neoplasms-
dc.subject.meshHumans-
dc.subject.meshLipopolysaccharides-
dc.subject.meshNF-kappa B-
dc.subject.meshNeoplasm Invasiveness-
dc.subject.meshReceptors, Urokinase Plasminogen Activator-
dc.subject.meshToll-Like Receptor 4-
dc.subject.meshTumor Cells, Cultured-
dc.subject.meshUrokinase-Type Plasminogen Activator-
dc.titleBacterial endotoxin enhances colorectal cancer cell adhesion and invasion through TLR-4 and NF-kappaB-dependent activation of the urokinase plasminogen activator system.en
dc.typeArticleen
dc.contributor.departmentDepartment of Academic Surgery, Cork University Hospital and University College Cork, Cork, Ireland. sdfkilleen@eircom.neten
dc.identifier.journalBritish journal of canceren
dc.description.provinceMunster-

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