Real-time optical imaging of primary tumor growth and multiple metastatic events in a pancreatic cancer orthotopic model.
Real-time optical imaging of primary tumor growth and multiple metastatic events in a pancreatic cancer orthotopic model.
复制标题
DOI：
--
复制
发表时间：
2002-03
期刊：
影响因子：
11.2
通讯作者：
M. Bouvet;Jinwei Wang;S. Nardin;Rounak Nassirpour;Meng Yang;E. Baranov;P. Jiang;A. Moossa;R. Hoffman
中科院分区：
文献类型：
--
作者：
M. Bouvet;Jinwei Wang;S. Nardin;Rounak Nassirpour;Meng Yang;E. Baranov;P. Jiang;A. Moossa;R. Hoffman
我们在这里实时报告遗传荧光胰腺肿瘤生长和转移到活体小鼠多个部位的全身光学成像。全身光学成像系统是体外的、非侵入性的。人胰腺肿瘤细胞系 BxPC-3 和 MiaPaCa-2 经过改造，可稳定表达高水平的维多利亚多管发光蛋白 (GFP)。通过手术将表达 GFP 的胰腺肿瘤细胞系作为组织碎片原位植入裸鼠胰腺体内。全身光学图像实时显示原发肿瘤的生长以及脾、肠、门淋巴结、大网膜和肝脏中发生的转移性病变的形成。打开动物的活体图像证实了全身图像的身份。全身图像用于实时定量测量每个器官中的肿瘤生长。活体成像用于量化肝脏和胃上微转移的生长。使用透射照明落射荧光显微镜或荧光灯箱进行全身成像，两者均配有热电冷却彩色 CCD 相机。强 GFP 荧光使简单、非侵入性和高选择性成像成为可能，从而可以对胰腺癌的肿瘤生长和多发转移形成进行详细的同步定量成像。 GFP 成像提供了对完整动物内恶性生长和扩散的前所未有的连续视觉监测，无需麻醉、底物注射、造影剂或其他成像方法所需的动物约束。本报告中提出的 GFP 成像技术将促进胰腺癌生长调节剂的研究，包括潜在化疗药物的抑制作用。
We report here whole-body optical imaging, in real time, of genetically fluorescent pancreatic tumors growing and metastasizing to multiple sites in live mice. The whole-body optical imaging system is external and noninvasive. Human pancreatic tumor cell lines, BxPC-3 and MiaPaCa-2, were engineered to stably express high-levels of the Aequorea victoria green fluorescent protein (GFP). The GFP-expressing pancreatic tumor cell lines were surgically orthotopically implanted as tissue fragments in the body of the pancreas of nude mice. Whole-body optical images visualized real-time primary tumor growth and formation of metastatic lesions that developed in the spleen, bowel, portal lymph nodes, omentum, and liver. Intravital images in the opened animal confirmed the identity of whole-body images. The whole-body images were used for real-time, quantitative measurement of tumor growth in each of these organs. Intravital imaging was used for quantification of growth of micrometastasis on the liver and stomach. Whole-body imaging was carried out with either a trans-illuminated epi-fluorescence microscope or a fluorescence light box, both with a thermoelectrically cooled color CCD camera. The simple, noninvasive, and highly selective imaging made possible by the strong GFP fluorescence allowed detailed simultaneous quantitative imaging of tumor growth and multiple metastasis formation of pancreatic cancer. The GFP imaging affords unprecedented continuous visual monitoring of malignant growth and spread within intact animals without the need for anesthesia, substrate injection, contrast agents, or restraint of animals required by other imaging methods. The GFP imaging technology presented in this report will facilitate studies of modulators of pancreatic cancer growth, including inhibition by potential chemotherapeutic agents.