A critical step in metastasis: in vivo analysis of intravasation at the primary tumor.

A critical step in metastasis: in vivo analysis of intravasation at the primary tumor.
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DOI:
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发表时间:
2000-05
期刊:
影响因子:
11.2
通讯作者:
J. Wyckoff;Joan G. Jones;J. Condeelis;J. Segall
J. Wyckoff;Joan G. Jones;J. Condeelis;J. Segall
中科院分区:
医学1区
文献类型:
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作者:
J. Wyckoff;Joan G. Jones;J. Condeelis;J. Segall

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详细评价肿瘤细胞转移的所有步骤对于评价控制转移的细胞机制至关重要。使用绿色荧光蛋白转染的转移性(MTLn 3)和非转移性(MTC)细胞系来自大鼠乳腺癌13762 NF,我们测量了血液中的肿瘤细胞密度,在肺中的单个肿瘤细胞,和肺转移。血液负荷与肺转移的相关性表明进入循环是转移的关键步骤。为了检查细胞在血管内渗过程中的行为,我们使用了绿色荧光蛋白技术,使用共聚焦显微镜在单个光学切片内观察这些细胞的延时图像。MTLn3和MTC细胞的原发性肿瘤的体内成像表明,转移性和非转移性细胞都是能动的,并显示出扩散活性。然而,转移性细胞显示出更大的朝向血管的取向和原发性肿瘤内更多数量的宿主细胞,而非转移性细胞在与血管相互作用时碎片化。这些结果表明,在原发性肿瘤中检测到转移性和非转移性细胞之间的内渗的主要差异,并说明了在体内直接可视化细胞特性用于解剖转移过程的价值。
Detailed evaluation of all steps in tumor cell metastasis is critical for evaluating the cell mechanisms controlling metastasis. Using green fluorescent protein transfectants of metastatic (MTLn3) and nonmetastatic (MTC) cell lines derived from the rat mammary adenocarcinoma 13762 NF, we have measured tumor cell density in the blood, individual tumor cells in the lungs, and lung metastases. Correlation of blood burden with lung metastases indicates that entry into the circulation is a critical step for metastasis. To examine cell behavior during intravasation, we have used green fluorescent protein technology to view these cells in time lapse images within a single optical section using a confocal microscope. In vivo imaging of the primary tumors of MTLn3 and MTC cells indicates that both metastatic and nonmetastatic cells are motile and show protrusive activity. However, metastatic cells show greater orientation toward blood vessels and larger numbers of host cells within the primary tumor, whereas nonmetastatic cells fragment when interacting with vessels. These results demonstrate that a major difference in intravasation between metastatic and nonmetastatic cells is detected in the primary tumor and illustrate the value of a direct visualization of cell properties in vivo for dissection of the metastatic process.