Lipopolysaccharide-induced metastatic growth is associated with increased angiogenesis, vascular permeability and tumor cell invasion
Lipopolysaccharide-induced metastatic growth is associated with increased angiogenesis, vascular permeability and tumor cell invasion
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DOI：
10.1002/ijc.10632
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发表时间：
2002-10-10
影响因子：
6.4
通讯作者：
Dong, ZY
中科院分区：
文献类型：
--
作者：
Harmey, JH;Bucana, CD;Dong, ZY
内毒素/脂多糖(LPS)是革兰氏阴性菌的细胞壁成分，是一种强有力的炎性刺激物质。我们之前曾报道，在小鼠肿瘤模型中，LIPS增加了实验性转移瘤的生长。在这里，我们研究了脂多糖暴露对转移的关键决定因素-血管生成、肿瘤细胞侵袭、血管通透性、一氧化氮合酶(NOS)和基质金属蛋白酶2(MMP2)表达的影响。荷4TI肺转移瘤的BALB/c小鼠腹腔注射(Ip)。注射10杯嘴唇或生理盐水。暴露于脂多糖可导致肺重量增加和胸膜病变发生率增加。在体内和体外，脂多糖均可促进血管生成。肺组织血管通透性在注射内毒素后18h明显增加。脂多糖增加肺肿瘤结节诱导型一氧化氮合酶(INOS)和MMP2的表达。4TI细胞经尾静脉注射绿色荧光蛋白(4TI-GFP)。与生理盐水对照组相比，嘴唇暴露可导致小鼠肺组织中4TI-GFP细胞数量增加，这种作用可被竞争性一氧化氮合酶抑制剂N-G甲基-L-精氨酸所阻断。脂多糖诱导的4TI实验性肺转移瘤的生长和转移与血管生成、血管通透性和肿瘤细胞的侵袭/迁移有关，iNOS的表达参与了脂多糖诱导的肺转移。(C)2002年Wiley-Liss，Inc.
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.