Lipopolysaccharide-induced metastatic growth is associated with increased angiogenesis, vascular permeability and tumor cell invasion.
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 microg 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.
Harmey
Judith H
JH
Department of Cell Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. jharmey@rcsi.ie
Bucana
Corazon D
CD
Lu
Weixin
W
Byrne
Anne Marie
AM
McDonnell
Susan
S
Lynch
Conor
C
Bouchier-Hayes
David
D
Dong
Zhongyun
Z
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002465:Cell Movement; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000494:pharmacology; D005260:Female; D006160:Guanosine Triphosphate / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary*; D008222:Lymphokines / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000139:chemically induced*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008070:Lipopolysaccharides; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D006160:Guanosine Triphosphate; D019001:Nitric Oxide Synthase; D020778:Matrix Metalloproteinase 2