Gene transfer of the vascular endothelial growth factor receptor flt-1 suppresses pulmonary metastasis associated with lung growth
Gene transfer of the vascular endothelial growth factor receptor flt-1 suppresses pulmonary metastasis associated with lung growth
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DOI：
10.1165/rcmb.2005-0092oc
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发表时间：
2005-12-01
影响因子：
6.4
通讯作者：
Crystal, RG
中科院分区：
文献类型：
--
作者：
Mae, M;O'Connor, TP;Crystal, RG
实体瘤转移的生长严重依赖于血管生成。我们假设一个“血管生成丰富”的环境，如肺切除术诱导的肺生长，将有利于肺转移瘤的生长，而抗血管生成基因的转移将抑制肿瘤的生长。BALB/c小鼠左肺切除后2周，右肺重量比对照组增加1.5倍（P < 0.0001）。我们的肺转移模型，静脉内施用β-半乳糖苷酶（β gal）标记的CT26.CL25结肠癌细胞，在施用后12天导致弥漫性转移。然而，如果在肿瘤细胞给药前1天进行左肺切除术，12天后右肺质量增加1.7倍（与对照组的右左肺相比，P < 0.001），β-gal活性更高（2.8倍，P < 0.05）。为了评估抗血管生成治疗，在肺切除术后第1天施用肿瘤细胞，第1天后施用5 × 101空斑形成单位的Adsflt（表达fit-1血管内皮生长因子[VEGF]受体的细胞外部分的Ad载体）。与对照相比，通过鼻内或静脉内途径接受Adsflt的小鼠显示出肺切除术诱导的肿瘤生长的抑制（P < 0.01，两种途径与对照相比）。肺切除术后的肺生长促进肺转移瘤的生长，但这可以用Adsflt抗血管生成治疗来抑制。
Growth of solid tumor metastases is critically dependent on angiogenesis. We hypothesized that an "angiogenic-rich" milieu, as in pneumonectomy-induced lung growth, would be conducive to growth of pulmonary metastases, and that transfer of an antiangio-genic gene would suppress tumor growth. Two weeks after left pneumonectomy in BALB/c mice, right lung mass increased 1.5-fold compared with controls (P < 0.0001). Our pulmonary metastases model, intravenous administration of beta-galactosidase (beta gal)marked CT26.CL25 colon carcinoma cells, resulted in diffuse metastases at 12 d after administration. However, if left pneumonectomy was performed I d before tumor cell administration, right lung mass was increased 1.7-fold after 12 d (P < 0.001 compared with the right left lung of controls), and beta gal activity was greater (2.8-fold, P < 0.05). To assess antiangiogenesis therapy, tumor cells were administered I d after pneumonectomy and 1 d later, 5 X 101 plaque-forming units of Adsflt (an Ad vector expressing the extracellular portion of the fit-1 vascular endothelial growth factor [VEGF] receptor) was administered. Compared with controls, mice receiving Adsflt via intranasal or intravenous routes showed suppression of pneumonectomy-induced tumor growth (P < 0.01, both routes compared with controls). Postpneumonectomy lung growth enhances growth of lung metastases, but this can be suppressed with Adsflt antiangiogenesis therapy.