Dual-color imaging of nascent blood vessels vascularizing pancreatic cancer in an orthotopic model demonstrates antiangiogenesis efficacy of gemcitabine
Dual-color imaging of nascent blood vessels vascularizing pancreatic cancer in an orthotopic model demonstrates antiangiogenesis efficacy of gemcitabine
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DOI：
10.1016/j.jss.2005.12.028
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发表时间：
2006-05-15
影响因子：
2.2
通讯作者：
Bouvet, M
中科院分区：
文献类型：
--
作者：
Amoh, Y;Li, LN;Bouvet, M
背景。最近，干细胞标记巢蛋白已被证明在巢蛋白驱动的绿色荧光蛋白（ND-GFP）转基因裸鼠的新生血管中表达。材料和方法。在本研究中，我们通过双色荧光成像观察了表达红色荧光蛋白的 MIA PaCa-2 人胰腺癌细胞系原位移植后 ND-GFP 转基因裸鼠中肿瘤血管生成的情况。肿瘤植入后第 3、6、10 和 13 天，小鼠接受 150 mg/kg/剂量的吉西他滨治疗。第14天，处死小鼠，计算平均新生血管密度和肿瘤体积，并与对照小鼠进行比较。结果。巢蛋白在生长的肿瘤中的增殖内皮细胞和新生血管中高度表达。免疫组织化学染色结果显示，CD31 共定位于表达 ND-GFP 的新生血管中。肿瘤中新生血管的密度很容易定量。吉西他滨显着降低了肿瘤中的平均新生血管密度并减小了肿瘤体积。结论。原位植入表达 RFP 的胰腺肿瘤细胞的 ND-GFP 裸鼠双色模型能够同时可视化和定量肿瘤血管生成和肿瘤体积。这些结果首次证明吉西他滨是胰腺癌中血管生成和肿瘤生长的抑制剂。该结果对吉西他滨治疗该病的临床应用具有重要意义。 (c) 2006 Elsevier Inc. 保留所有权利。
Background. The stem cell marker nestin recently has been shown to be expressed in nascent blood vessels in nestin-driven green fluorescent protein (ND-GFP) transgenic nude mice.Materials and methods. In the present study, we visualized by dual-color fluorescence imaging tumor angiogenesis in the ND-GFP transgenic nude mice after orthotopic transplantation of the MIA PaCa-2 human pancreatic cancer line expressing red fluorescent protein. Mice were treated with gemcitabine at 150 mg/kg/dose on days 3, 6, 10, and 13 after tumor implantation. At day 14, mice were sacrificed and mean nascent blood vessel density and tumor volume were calculated and compared to control mice.Results. Nestin was highly expressed in proliferating endothelial cells and nascent blood vessels in the growing tumor. Results of immunohistochemical staining showed that CD31 co-localized in ND-GFP-expressing nascent blood vessels. The density of nascent blood vessels in the tumor was readily quantitated. Gemcitabine significantly decreased the mean nascent blood vessel density in the tumor as well as decreased tumor volume.Conclusion. The dual-color model of the ND-GFP nude mouse orthotopically implanted with RFP-expressing pancreatic tumor cells enabled the simultaneous visualization and quantitation of tumor angiogenesis and tumor volume. These results demonstrated for the first time that gemcitabine is an inhibitor of angiogenesis as well as tumor growth in pancreatic cancer. The results have important implications for the clinical application of gemcitabine in this disease. (c) 2006 Elsevier Inc. All rights reserved.