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 LIPS 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 4TI lung metastases were given an intraperitoneal (i.p.) injection of 10 mug LIPS 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. 4TI cells transfected with green fluorescent protein (4TI-GFP) were injected via lateral tail vein. LIPS exposure resulted in increased numbers 4TI -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 4TI experimental lung metastases is associated with increased angiogenesis, vascular permeability and tumor cell invasion/migration with iNOS expression implicated in LPS-induced metastasis. (C) 2002 Wiley-Liss, Inc.