Soluble interleukin 6 receptor (sIL-6R) mediates colonic tumor cell adherence to the vascular endothelium: a mechanism for metastatic initiation?

Hdl Handle:
http://hdl.handle.net/10147/209019
Title:
Soluble interleukin 6 receptor (sIL-6R) mediates colonic tumor cell adherence to the vascular endothelium: a mechanism for metastatic initiation?
Authors:
Dowdall, J F; Winter, D C; Andrews, E; Laug, W E; Wang, J H; Redmond, H P
Affiliation:
Department of Academic Surgery, Cork University Hospital, Wilton, Ireland.
Citation:
J Surg Res. 2002 Sep;107(1):1-6.
Journal:
The Journal of surgical research
Issue Date:
3-Feb-2012
URI:
http://hdl.handle.net/10147/209019
PubMed ID:
12384057
Abstract:
The mechanisms by which surgery increases metastatic proliferation remain poorly characterized, although endotoxin and immunocytes play a role. Recent evidence suggests that endothelial adherence of tumor cells may be important in the formation of metastases. Soluble receptors of interleukin-6 (sIL-6R) shed by activated neutrophils exert IL-6 effects on endothelial cells, which are unresponsive under normal circumstances. This study examined the hypothesis that sIL-6R released by surgical stress increases tumor cell adherence to the endothelium. Neutrophils (PMN) were stimulated with lipopolysaccharide, C-reactive protein (CRP), and tumor necrosis factor-alpha. Soluble IL-6R release was measured by enzyme-linked immunosorbent assay. Colonic tumor cells transfected with green fluorescent protein and endothelial cells were exposed to sIL-6R, and tumor cell adherence and transmigration were measured by fluorescence microscopy. Basal release of sIL-6R from PMN was 44.7 +/- 8.2 pg/ml at 60 min. This was significantly increased by endotoxin and CRP (131 +/- 16.8 and 84.1 +/- 5.3, respectively; both P < 0.05). However, tumor necrosis factor-alpha did not significantly alter sIL-6R release. Endothelial and tumor cell exposure to sIL-6R increased tumor cell adherence by 71.3% within 2 h but did not significantly increase transmigration, even at 6 h. Mediators of surgical stress induce neutrophil release of a soluble receptor for IL-6 that enhances colon cancer cell endothelial adherence. Since adherence to the endothelium is now considered to be a key event in metastatic genesis, these findings have important implications for colon cancer treatment strategies.
Language:
eng
MeSH:
Cell Adhesion/physiology; Cell Movement; Cells, Cultured; Colonic Neoplasms/*physiopathology/secondary; Endothelium, Vascular/*physiopathology; Humans; Intercellular Adhesion Molecule-1/metabolism; Neoplasm Metastasis/physiopathology; Receptors, Interleukin-6/*metabolism; Solubility
ISSN:
0022-4804 (Print); 0022-4804 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorDowdall, J Fen_GB
dc.contributor.authorWinter, D Cen_GB
dc.contributor.authorAndrews, Een_GB
dc.contributor.authorLaug, W Een_GB
dc.contributor.authorWang, J Hen_GB
dc.contributor.authorRedmond, H Pen_GB
dc.date.accessioned2012-02-03T15:10:05Z-
dc.date.available2012-02-03T15:10:05Z-
dc.date.issued2012-02-03T15:10:05Z-
dc.identifier.citationJ Surg Res. 2002 Sep;107(1):1-6.en_GB
dc.identifier.issn0022-4804 (Print)en_GB
dc.identifier.issn0022-4804 (Linking)en_GB
dc.identifier.pmid12384057en_GB
dc.identifier.urihttp://hdl.handle.net/10147/209019-
dc.description.abstractThe mechanisms by which surgery increases metastatic proliferation remain poorly characterized, although endotoxin and immunocytes play a role. Recent evidence suggests that endothelial adherence of tumor cells may be important in the formation of metastases. Soluble receptors of interleukin-6 (sIL-6R) shed by activated neutrophils exert IL-6 effects on endothelial cells, which are unresponsive under normal circumstances. This study examined the hypothesis that sIL-6R released by surgical stress increases tumor cell adherence to the endothelium. Neutrophils (PMN) were stimulated with lipopolysaccharide, C-reactive protein (CRP), and tumor necrosis factor-alpha. Soluble IL-6R release was measured by enzyme-linked immunosorbent assay. Colonic tumor cells transfected with green fluorescent protein and endothelial cells were exposed to sIL-6R, and tumor cell adherence and transmigration were measured by fluorescence microscopy. Basal release of sIL-6R from PMN was 44.7 +/- 8.2 pg/ml at 60 min. This was significantly increased by endotoxin and CRP (131 +/- 16.8 and 84.1 +/- 5.3, respectively; both P < 0.05). However, tumor necrosis factor-alpha did not significantly alter sIL-6R release. Endothelial and tumor cell exposure to sIL-6R increased tumor cell adherence by 71.3% within 2 h but did not significantly increase transmigration, even at 6 h. Mediators of surgical stress induce neutrophil release of a soluble receptor for IL-6 that enhances colon cancer cell endothelial adherence. Since adherence to the endothelium is now considered to be a key event in metastatic genesis, these findings have important implications for colon cancer treatment strategies.en_GB
dc.language.isoengen_GB
dc.subject.meshCell Adhesion/physiologyen_GB
dc.subject.meshCell Movementen_GB
dc.subject.meshCells, Cultureden_GB
dc.subject.meshColonic Neoplasms/*physiopathology/secondaryen_GB
dc.subject.meshEndothelium, Vascular/*physiopathologyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshIntercellular Adhesion Molecule-1/metabolismen_GB
dc.subject.meshNeoplasm Metastasis/physiopathologyen_GB
dc.subject.meshReceptors, Interleukin-6/*metabolismen_GB
dc.subject.meshSolubilityen_GB
dc.titleSoluble interleukin 6 receptor (sIL-6R) mediates colonic tumor cell adherence to the vascular endothelium: a mechanism for metastatic initiation?en_GB
dc.contributor.departmentDepartment of Academic Surgery, Cork University Hospital, Wilton, Ireland.en_GB
dc.identifier.journalThe Journal of surgical researchen_GB
dc.description.provinceMunster-
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