Dual-color imaging of nascent angiogenesis and its inhibition in liver metastases of pancreatic cancer.
Dual-color imaging of nascent angiogenesis and its inhibition in liver metastases of pancreatic cancer.
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发表时间：
2006-09
影响因子：
2
通讯作者：
Y. Amoh;Chisa Nagakura;A. Maitra;A. Moossa;K. Katsuoka;R. Hoffman;M. Bouvet
中科院分区：
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作者：
Y. Amoh;Chisa Nagakura;A. Maitra;A. Moossa;K. Katsuoka;R. Hoffman;M. Bouvet
如前所述，干细胞标记物巢蛋白在转基因巢蛋白驱动绿色荧光蛋白（ND-GFP）裸鼠新生血管中表达。该小鼠模型最近被用于评估胰腺癌原位模型中原发肿瘤的血管生成。本研究用双色荧光成像技术观察了表达红色荧光蛋白（RFP）的低传代xPA-1人胰腺癌细胞脾注射后ND-GFP转基因裸鼠胰腺癌肝转移新生血管生成的情况。ND-GFP在生长中的肝转移瘤中增殖内皮细胞和新生血管中高表达。免疫组化染色显示CD31在表达nd - gfp的新生血管中共定位。肿瘤新生血管的密度很容易定量。吉西他滨显著降低胰腺肝转移患者新生血管的平均密度。综上所述，表达rfp的胰腺癌肝转移裸鼠ND-GFP双色模型能够同时可视化和定量新生血管生成及其对血管生成抑制剂的反应。该模型将有助于了解胰腺癌肝转移血管生成的机制，并有助于发现有效的新抑制剂。
As previously shown, the stem cell marker nestin is expressed in nascent blood vessels in transgenic nestin-driven green fluorescent protein (ND-GFP) nude mice. This mouse model was recently utilized to evaluate angiogenesis in primary tumors in an orthotopic model of pancreatic cancer. In the present study, nascent angiogenesis of pancreatic cancer liver metastasis in the ND-GFP transgenic nude mice after splenic injection of low-passage xPA-1 human pancreatic cancer cells expressing red fluorescent protein (RFP) was visualized by dual-color fluorescence imaging. ND-GFP was highly expressed in proliferating endothelial cells and nascent blood vessels in the growing liver metastasis. 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 pancreatic liver metastases. In conclusion, the dual-color model of the ND-GFP nude mouse with RFP-expressing pancreatic cancer liver metastases, enabled the simultaneous visualization and quantitation of nascent angiogenesis and its response to angiogenesis inhibitors. This model will be useful for understanding the mechanism of angiogenesis of pancreatic cancer liver metastasis and for the discovery of effective new inhibitors of this process.