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Lipopolysaccharide‐induced metastatic growth is associated with increased angiogenesis, vascular permeability and tumor cell invasion
Author(s) -
Harmey Judith H.,
Bucana Corazon D.,
Lu Weixin,
Byrne Anne Marie,
McDonnell Susan,
Lynch Conor,
BouchierHayes David,
Dong Zhongyun
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10632
Subject(s) - angiogenesis , lipopolysaccharide , nitric oxide synthase , mmp2 , vascular permeability , in vivo , metastasis , nitric oxide , biology , pathology , cancer research , medicine , immunology , endocrinology , cancer , microbiology and biotechnology
Endotoxin/lipopolysaccharide (LPS), a cell wall component of Gram‐negative bacteria, is a potent inflammatory stimulus. We previously reported that LPS increased the growth of experimental metastases in a murine tumor model. Here, we examined the effect of LPS exposure on key determinants of metastasis—angiogenesis, tumor cell invasion, vascular permeability, nitric oxide synthase (NOS) and matrix metalloproteinase 2 (MMP2) expression. BALB/c mice bearing 4T1 lung metastases were given an intraperitoneal (i.p.) injection of 10 μg LPS or saline. LPS exposure resulted in increased lung weight and incidence of pleural lesions. LPS increased angiogenesis both in vivo and in vitro . Vascular permeability in lung tissue was increased 18 hr after LPS injection. LPS increased inducible nitric oxide synthase (iNOS) and MMP2 expression in lung tumor nodules. 4T1 cells transfected with green fluorescent protein (4T1‐GFP) were injected via lateral tail vein. LPS exposure resulted in increased numbers of 4T1‐GFP cells in mouse lung tissue compared to saline controls, an effect blocked by the competitive NOS inhibitor, N G methyl‐L‐arginine (NMA). LPS‐induced growth and metastasis of 4T1 experimental lung metastases is associated with increased angiogenesis, vascular permeability and tumor cell invasion/migration with iNOS expression implicated in LPS‐induced metastasis. © 2002 Wiley‐Liss, Inc.