摘要
瞄准:学习巨噬细胞的角色在在一只老鼠的肿瘤生长的导致切除术的加速肝的转移建模的肝的煽动性的蛋白质(MIP )-2。方法:在 50% 肝切除术以后, 1x10 (5 ) CT26.WT 房间被植入进 syngeneic balb/c 老鼠(PHx ) 的左肝脑叶。另外的动物与抵销 MIP-2 (PHx+mAB ) 的单音的同种细胞的抗体(MAB452 ) 被对待。将切除得非并且 non-mAB-treated 老鼠(反对) 用作控制。在 7 d 以后,象房间增长,肿瘤生长,和 CXCR-2 表示一样的肿瘤血管生成和微循环用生活期内萤光显微镜检查,组织学,免疫组织化学,和流动被分析血细胞计数。结果:增加的部分肝切除术(P【0.05 ) 肿瘤房间上的 MIP-2 受体 CXCR-2 的表示什么时候与将切除得非的控制相比,并且显著地加速了(P【0.05 ) 血管生成和转移瘤生长。(P【0.05 ) 由 MAB452 处理的 MIP-2 的中立化显著地压抑 CXCR-2 表示。进一步, MIP-2 的封锁减少了 angiogenic 反应(P【0.05 ) 并且禁止了肿瘤生长(P【0.05 ) 。兴趣,肝导致切除术的 hepatocyte 增长没被 anti-MIP-2 处理完成。结论:MIP-2 显著地贡献肝颜色的导致切除术的加速表面的 CT26.WT 肝的转移生长。
AIM: To study the role of macrophage inflammatory protein (HIP)-2 in liver resection-induced acceleration of tumor growth in a mouse model of hepatic metastasis.
METHODS: After a 50% hepatectomy, 1×10^5 CT26.WT cells were implanted into the left liver lobe of syngeneic balb/c mice (PHx). Additional animals were treated with a monoclonal antibody (HAB452) neutralizing HIP-2 (PHx+mAB). Non-resected and non-mAB-treated mice (Con) served as controls. After 7 d, tumor angiogenesis and microcirculation as well as cell proliferation, tumor growth, and CXCR-2 expression were analyzed using in- travital fluorescence microscopy, histology, immunohisto- chemistry, and flow cytometry.
RESULTS: Partial hepatectomy increased (P〈0.05)the expression of the HIP-2 receptor CXCR-2 on tumor cells when compared with non-resected controls, and markedly accelerated (P〈 0.05) angiogenesis and metastatic tumor growth. Neutralization of HIP-2 by HAB452 treatment significantly (P〈 0.05) depressed CXCR-2 expression. Further, the blockade of MIP-2 reduced the angiogenic response (P〈 0.05) and inhibited tumor growth (P〈 0.05). Of interest, liver resection-induced hepatocyte proliferation was not effected by anti-HIP-2 treatment.
CONCLUSION: HIP-2 significantly contributes to liver resection-induced acceleration of colorectal CT26.WT hepatic metastasis growth.
基金
Supported by the grants of the Research Committee
the Medical Faculty of the University of Saarland,No.HOMFOR-A/2003/1
关键词
巨噬细胞
炎性蛋白-2
肝切除手术
加速度
肿瘤生长因子
Chemokines
MIP-2
Liver resection
Partial hepatectomy
Liver regeneration
Metastatic tumor growth
Angiogenesis
Microcirculation