In vivo selection of highly metastatic cells from surgical specimens of different primary human colon carcinomas implanted into nude mice.
In vivo selection of highly metastatic cells from surgical specimens of different primary human colon carcinomas implanted into nude mice.
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DOI：
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发表时间：
1988-04
期刊：
影响因子：
11.2
通讯作者：
K. Morikawa;S. Walker;J. Jessup;I. Fidler
中科院分区：
文献类型：
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作者：
K. Morikawa;S. Walker;J. Jessup;I. Fidler
这些研究的目的是从异质性原发性人结肠癌（HCC）中选择和分离具有增加的肝转移潜力的细胞。将来源于分类为Dukes'B2期的原发性HCC的细胞直接在培养物中建立或注射到裸鼠的皮下组织、盲肠或脾脏中。将逐渐生长的肿瘤切除、分离并在培养物中建立。在移植到裸鼠的盲肠或脾脏中之后，来自所有四个系的细胞仅产生少数肝肿瘤灶。将来自少数肝转移的HCC细胞在培养物中扩增，然后注射到裸鼠的脾脏中，以提供进一步选择循环的来源。随着每个连续的体内选择循环，分离的增殖细胞的转移能力增加。四个周期的选择产生的细胞系在裸鼠中具有非常高的转移效率。在使用另一种分类为Dukes'D期的原发性HCC的平行研究中，我们分离了在裸鼠中高度转移的细胞系。在肝脏中生长的连续选择循环增加了HCC细胞的转移特性，尽管程度低于Dukes的B2期HCC。HCC细胞产生肝转移的能力不是由于在肝脏中的简单捕获。使用[125 I]碘脱氧尿苷标记的肿瘤细胞进行的体内分布研究显示，在注射到脾脏后不久，具有低或高转移特性的相当数量的细胞在肝脏中被捕获。注射后24小时，低转移性和高转移性细胞之间的差异变得明显，到72小时，只有高转移性细胞在肝脏中存活。这些结果表明，肝癌细胞的肝转移是一个选择性的过程，裸鼠模型可以用于分离高转移性肝癌细胞和研究相关的宿主器官的因素，调节转移的发病机制。
The purpose of these studies was to select and isolate cells with increased liver-metastasizing potential from heterogeneous primary human colon carcinomas (HCCs). Cells derived from a primary HCC classified as Dukes' stage B2 were directly established in culture or were injected into the subcutis, cecum, or spleen of nude mice. Progressively growing tumors were excised, dissociated, and established in culture. Subsequent to implantation into the cecum or spleen of nude mice, cells from all four lines produced only a few liver tumor foci. HCC cells from the few liver metastases were expanded in culture and then injected into the spleen of nude mice to provide a source for further cycles of selection. With each successive in vivo selection cycle, the metastatic ability of the isolated propagated cells increased. Four cycles of selection yielded cell lines with a very high metastatic efficiency in nude mice. In parallel studies using another primary HCC classified as Dukes' stage D, we isolated cell lines that were highly metastatic in nude mice. Successive selection cycles for growth in the liver increased the metastatic properties of the HCC cells, albeit to a lesser extent than it did those of the Dukes' B2 stage HCC. The ability of the HCC cells to produce liver metastases was not due to simple trapping in the liver. In vivo distribution studies using [125I] iododeoxyuridine-labeled tumor cells revealed that, shortly after injection into the spleen, a comparable number of cells with either low or high metastatic properties arrested in the liver. The differences between the low- and high-degree metastatic cells became apparent by 24 h after injection and, by 72 h, only highly metastatic cells survived in the liver. These results demonstrate that hepatic metastasis by HCC cells is a selective process and that the nude mouse model can be useful for isolating highly metastatic HCC cells and for studying the relevant host organ factors that regulate the pathogenesis of metastasis.