Tumor cell adhesion to endothelial cells is increased by endotoxin via an upregulation of beta-1 integrin expression.
AffiliationDepartment of Surgery, Cork University Hospital, Cork, Ireland., firstname.lastname@example.org
Cell Adhesion/*drug effects
Endothelium, Vascular/drug effects/*metabolism
NF-kappa B/antagonists & inhibitors/metabolism
Tumor Cells, Cultured
MetadataShow full item record
CitationJ Surg Res. 2001 May 1;97(1):14-9.
JournalThe Journal of surgical research
AbstractBACKGROUND: Recent studies have demonstrated that metastatic disease develops from tumor cells that adhere to endothelial cells and proliferate intravascularly. The beta-1 integrin family and its ligand laminin have been shown to be important in tumor-to-endothelial cell adhesion. Lipopolysaccharide (LPS) has been implicated in the increased metastatic tumor growth that is seen postoperatively. We postulated that LPS increases tumor cell expression of beta-1 integrins and that this leads to increased adhesion. METHODS: The human metastatic colon cancer cell line LS174T was labeled with an enhanced green fluorescent protein (eGFP) using retroviral transfection. Cell cultures were treated with LPS for 1, 2, and 4 h (n = 6 each) and were subsequently cocultured for 30 or 120 min with confluent human umbilical vein endothelial cells (HUVECs), to allow adherence. Adherent tumor cells were counted using fluorescence microscopy. These experiments were carried out in the presence or absence of a functional blocking beta-1 integrin monoclonal antibody (4B4). Expression of beta-1 integrin and laminin on tumor and HUVECs was assessed using flow cytometric analysis. Tumor cell NF-kappaB activation after incubation with LPS was measured. RESULTS: Tumor cell and HUVEC beta-1 integrin expression and HUVEC expression of laminin were significantly (P < 0.05) enhanced after incubation with LPS. Tumor cell adhesion to HUVECs was significantly increased. Addition of the beta-1 integrin blocking antibody reduced tumor cell adhesion to control levels. LPS increased tumor cell NF-kappaB activation. CONCLUSIONS: Exposure to LPS increases tumor cell adhesion to the endothelium through a beta-1 integrin-mediated pathway that is NF-kappaB dependent. This may provide a target for immunotherapy directed at reducing postoperative metastatic tumor growth.
- Ionizing radiation induces up-regulation of functional beta1-integrin in human lung tumour cell lines in vitro.
- Authors: Cordes N, Blaese MA, Meineke V, Van Beuningen D
- Issue date: 2002 May
- Activation of microvascular endothelium by eicosanoid 12(S)-hydroxyeicosatetraenoic acid leads to enhanced tumor cell adhesion via up-regulation of surface expression of alpha v beta 3 integrin: a posttranscriptional, protein kinase C- and cytoskeleton-dependent process.
- Authors: Tang DG, Diglio CA, Honn KV
- Issue date: 1994 Feb 15
- Leukocyte-endothelial interaction is augmented by high glucose concentrations and hyperglycemia in a NF-kB-dependent fashion.
- Authors: Morigi M, Angioletti S, Imberti B, Donadelli R, Micheletti G, Figliuzzi M, Remuzzi A, Zoja C, Remuzzi G
- Issue date: 1998 May 1
- Hypertonic saline impedes tumor cell-endothelial cell interaction by reducing adhesion molecule and laminin expression.
- Authors: Shields CJ, Winter DC, Wang JH, Andrews E, Laug WE, Redmond HP
- Issue date: 2004 Jul
- Tetramethylpyrazine suppresses interleukin-8 expression in LPS-stimulated human umbilical vein endothelial cell by blocking ERK, p38 and nulear factor-kappaB signaling pathways.
- Authors: Li XY, He JL, Liu HT, Li WM, Yu C
- Issue date: 2009 Aug 17