Over-expression of human CD44s in murine 3T3 cells: selection against during primary tumorigenesis and selection for during micrometastasis.
Over-expression of human CD44s in murine 3T3 cells: selection against during primary tumorigenesis and selection for during micrometastasis.
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鼠 3T3 细胞中人类 CD44 的过度表达：原发性肿瘤发生期间的选择和微转移期间的选择。
DOI：
10.1023/a:1006568103588
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发表时间：
1998
影响因子：
4
通讯作者：
Culp,LA
中科院分区：
文献类型：
--
作者：
Kogerman,P;Sy,MS;Culp,LA
将高表达启动子调控的人CD44标准亚型(HCD44s)基因导入Balb/c 3T3细胞，观察其在裸鼠皮下的致瘤和转移能力。三个转染体中有一个是致瘤的。HCD44s在使用该致瘤克隆的大型原发肿瘤细胞中表达缺失。这些肿瘤具有极强的侵袭性，可向多个部位转移，包括肠系膜、胃、肝脏、横隔膜、胰腺和肺。微转移细胞重新表达hCD44s，这与其在转移级联反应的早期步骤中的重要性一致。HCD44s在转移灶中不表达，很可能在微转移灶向转移灶生长的过程中丢失。因此，hCD44s在小鼠3T3细胞中的表达在特定的病例中确实诱导了肿瘤的发生，与原发或继发肿瘤的侵袭性生长不相容，并且有利于转移扩散的早期步骤。这些结果表明，CD44s是一种新型的转移分子，它不利于肿瘤的生长，只有在肿瘤细胞向远处器官转移的过程中才具有暂时的优势。
Human CD44 standard isoform (hCD44s) cDNA regulated by a high-expressing promoter was transfected into Balb/c 3T3 cells and the tumorigenic and metastatic capacities of the transfectants were investigated in nude mice at the subcutaneous site. One of three transfectants was tumorigenic. hCD44s expression was lost in the cells of large primary tumors using this tumorigenic clone. These tumors were extremely aggressive giving overt metastases and micrometastases to several sites including mesentery, stomach, liver, diaphragm, pancreas and lung. Micrometastatic cells re-expressed hCD44s, consistent with its importance for early steps in the metastatic cascade. hCD44s was not expressed in overt metastases; most probably the expression was lost during the outgrowth of micrometastases into overt metastatic tumors. Thus hCD44s expression in murine 3T3 cells does induce tumorigenicity in select cases, is not compatible with aggressive outgrowth of primary or secondary tumors, and is advantageous for early steps in metastatic spread. These results suggest that CD44s is an example of a novel type of ‘metastasis’ molecule that is disadvantageous for tumor growth and is only transiently advantageous during metastatic spreading of tumor cells to distant organs.