Real-time imaging of lymphogenic metastasis in orthotopic human breast cancer
Real-time imaging of lymphogenic metastasis in orthotopic human breast cancer
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DOI：
10.1158/0008-5472.can-06-0728
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发表时间：
2006-08-15
期刊：
影响因子：
11.2
通讯作者：
Seger, Dalia
中科院分区：
文献类型：
--
作者：
Dadiani, Maya;Kalchenko, Vyacheslav;Seger, Dalia
转移到区域淋巴结是肿瘤细胞扩散的最早事件之一，是预测癌症患者生存的最重要的预后因素。肿瘤细胞通过淋巴系统扩散的实时体内成像可以增强我们对转移过程的理解。在此，我们描述了使用体内荧光显微镜成像来监测严重联合免疫缺陷小鼠原位人乳腺癌MDA-MB-231肿瘤的淋巴系统转移的进展以及自发转移的过程。利用表达高水平红色荧光蛋白的细胞，实现腹股沟淋巴结转移癌细胞的高分辨率非侵入性可视化。对这些淋巴结的顺序成像显示，肿瘤细胞最初通过淋巴系统侵入被膜下窦，然后侵入结节的实质。FITC-葡聚糖注射身份。在肿瘤区域，能够同时跟踪以绿色标记的淋巴管，并在这些血管内散布红色癌细胞。淋巴管中自发转移细胞的快速快照监测了少数肿瘤细胞的移动和聚集在淋巴管连接处的团块的发展。肿瘤中高间质液体压(IFP)的定量和FITC-葡聚糖快速引流到瘤周淋巴管的速度表明IFP诱导了淋巴系统的血管内流。这项工作提供了前所未有的实时荧光图像，可能有助于阐明自发淋巴转移过程中发生的步骤。
Metastatic spread to regional lymph nodes is one of the earliest events of tumor cell dissemination and presents a most significant prognostic factor for predicting survival of cancer patients. Real-time in vivo imaging of the spread of tumor cells through the lymphatic system can enhance our understanding of the metastatic process. Herein, we describe the use of in vivo fluorescence microscopy imaging to monitor the progression of lymph node metastasis as well as the course of spontaneous metastasis through the lymphatic system of orthotopic MDA-MB-231 human breast cancer tumors in severe combined immunodeficient mice. High-resolution noninvasive visualization of metastasizing cancer cells in the inguinal lymph nodes was achieved using cells expressing high levels of red fluorescent protein. Sequential imaging of these lymph nodes revealed the initial invasion of the tumor cells through the lymphatic system into the subcapsular sinuses followed by intrusion into the parenchyma of the nodes. FITC-dextran injected i.d. in the tumor area enabled simultaneous tracking of lymphatic vessels, labeled in green, and disseminated red cancer cells within these vessels. Fast snapshots of spontaneously metastasizing cells in the lymphatic vessels monitored the movement of a few tumor cells and the development of clumps clustered at lymphatic vessel junctions. Quantification of high interstitial fluid pressure (IFP) in the tumors and fast drainage rates of the FITC-dextran into the peritumoral lymphatic vessels suggested an IFP-induced intravasation into the lymphatic system. This work presents unprecedented live fluorescence images that may help to clarify the steps occurring in the course of spontaneous lymphogenic metastasis.