Endotoxin/lipopolysaccharide activates NF-kappa B and enhances tumor cell adhesion and invasion through a beta 1 integrin-dependent mechanism.
Authors
Wang, Jiang HuaiManning, Brian J
Wu, Qiong Di
Blankson, Siobhan
Bouchier-Hayes, D
Redmond, H Paul
Affiliation
Department of Academic Surgery, National University of Ireland, Cork University, Hospital, Ireland. jh.wang@ucc.i.eIssue Date
2012-02-03T15:09:53ZMeSH
Adjuvants, Immunologic/*pharmacologyAntigens, CD14/biosynthesis/metabolism/pharmacology
Antigens, CD29/biosynthesis/*physiology
Cell Adhesion/immunology
Cell Membrane/immunology/metabolism
Cell Movement/*immunology
Endotoxins/*pharmacology
Humans
I-kappa B Proteins/genetics
Integrin alphaVbeta3/biosynthesis
Lipopolysaccharides/*pharmacology
NF-kappa B/antagonists & inhibitors/*metabolism
Peptides/pharmacology
Signal Transduction/immunology
Solubility
Transfection
Tumor Cells, Cultured/immunology/metabolism/*pathology
Up-Regulation/immunology
Metadata
Show full item recordCitation
J Immunol. 2003 Jan 15;170(2):795-804.Journal
Journal of immunology (Baltimore, Md. : 1950)PubMed ID
12517943Abstract
Beta(1) integrins play a crucial role in supporting tumor cell attachment to and invasion into the extracellular matrix. Endotoxin/LPS introduced by surgery has been shown to enhance tumor metastasis in a murine model. Here we show the direct effect of LPS on tumor cell adhesion and invasion in extracellular matrix proteins through a beta(1) integrin-dependent pathway. The human colorectal tumor cell lines SW480 and SW620 constitutively expressed high levels of the beta(1) subunit, whereas various low levels of alpha(1), alpha(2), alpha(4), and alpha(6) expression were detected. SW480 and SW620 did not express membrane-bound CD14; however, LPS in the presence of soluble CD14 (sCD14) significantly up-regulated beta(1) integrin expression; enhanced tumor cell attachment to fibronectin, collagen I, and laminin; and strongly promoted tumor cell invasion through the Matrigel. Anti-beta(1) blocking mAbs (4B4 and 6S6) abrogated LPS- plus sCD14-induced tumor cell adhesion and invasion. Furthermore, LPS, when combined with sCD14, resulted in NF-kappaB activation in both SW480 and SW620 cells. Inhibition of the NF-kappaB pathway significantly attenuated LPS-induced up-regulation of beta(1) integrin expression and prevented tumor cell adhesion and invasion. These results provide direct evidence that although SW480 and SW620 cells do not express membrane-bound CD14, LPS in the presence of sCD14 can activate NF-kappaB, up-regulate beta(1) integrin expression, and subsequently promote tumor cell adhesion and invasion. Moreover, LPS-induced tumor cell attachment to and invasion through extracellular matrix proteins is beta(1) subunit-dependent.Language
engISSN
0022-1767 (Print)0022-1767 (Linking)
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