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首页> 外文会议>Conference on Optical Diagnostics of Living Cells Ⅴ, Jan 23-25, 2002, San Jose, USA >Fluorescence imaging of angiogenesis in green fluorescent protein-expressing tumors
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Fluorescence imaging of angiogenesis in green fluorescent protein-expressing tumors

机译：绿色荧光蛋白表达肿瘤中血管生成的荧光成像

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摘要

The development of therapeutics for the control of tumor angiogenesis requires a simple, reliable in vivo assay for tumor-induced vascularization. For this purpose, we have adapted the orthotopic implantation model of angiogenesis by using human and rodent tumors genetically tagged with Aequorea victoria green fluorescent protein (GFP) for grafting into nude mice. Genetically-fluorescent tumors can be readily imaged in vivo. The non-luminous induced capillaries are clearly visible against the bright tumor fluorescence examined either intravitally or by whole-body luminance in real time. Fluorescence shadowing replaces the laborious histological techniques for determining blood vessel density. High-level GFP-expressing tumor cell lines made it possible to acquire the high-resolution real-time fluorescent optical images of angiogenesis in both primary tumors and their metastatic lesions in various human and rodent tumor models by means of a light-based imaging system. Intravital images of angiogenesis onset and development were acquired and quantified from a GFP-expressing orthotopically-growing human prostate tumor over a 19-day period. Whole-body optical imaging visualized vessel density increasing linearly over a 20-week period in orthotopically-growing, GFP-expressing human breast tumor MDA-MB-435. Vessels in an orthotopically-growing GFP-expressing Lewis lung carcinoma tumor were visualized through the chest wall via a reversible skin flap. These clinically-relevant angiogenesis mouse models can be used for real-time in vivo evaluation of agents inhibiting or promoting tumor angiogenesis in physiological micro-environments.
机译：用于控制肿瘤血管生成的治疗剂的开发需要用于肿瘤诱导的血管形成的简单，可靠的体内测定。为了这个目的，我们通过使用经维多利亚水母发光管绿色荧光蛋白（GFP）基因标记的人和啮齿类动物移植到裸鼠中来适应血管新生的原位植入模型。遗传荧光肿瘤可以在体内轻松成像。相对于活体检查或通过全身亮度实时检查的明亮肿瘤荧光，非发光诱导的毛细血管清晰可见。荧光阴影取代了费力的组织学技术来确定血管密度。高水平表达GFP的肿瘤细胞系通过基于光学的成像系统，可以获取各种人类和啮齿动物肿瘤模型中原发性肿瘤及其转移灶中血管生成的高分辨率实时荧光光学图像。在19天的时间内，从表达GFP的原位生长的人类前列腺肿瘤中获取并量化了血管生成开始和发展的玻璃体内图像。全身光学成像可以观察到在原位生长的表达GFP的人乳腺肿瘤MDA-MB-435中，血管密度在20周内呈线性增加。在原位生长的表达GFP的Lewis肺癌肿瘤中，通过可逆的皮瓣通过胸壁观察血管。这些与临床相关的血管生成小鼠模型可用于实时体内评估在生理微环境中抑制或促进肿瘤血管生成的药物。

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