Kogerman P, Sy M S, Culp L A
Department of Molecular Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.
Clin Exp Metastasis. 1998 Jan;16(1):83-93. doi: 10.1023/a:1006568103588.
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.
将受高表达启动子调控的人类CD44标准异构体（hCD44s）cDNA转染到Balb/c 3T3细胞中，并在裸鼠皮下部位研究转染子的致瘤和转移能力。三个转染子中有一个具有致瘤性。使用该致瘤性克隆，在大的原发性肿瘤细胞中hCD44s表达缺失。这些肿瘤极具侵袭性，可向包括肠系膜、胃、肝脏、膈肌、胰腺和肺在内的多个部位发生明显转移和微转移。微转移细胞重新表达hCD44s，这与其在转移级联早期步骤中的重要性一致。hCD44s在明显转移灶中不表达；很可能在微转移灶发展为明显转移瘤的过程中表达丢失。因此，hCD44s在鼠3T3细胞中的表达在某些情况下确实会诱导致瘤性，与原发性或继发性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“转移”分子的例子，它对肿瘤生长不利，仅在肿瘤细胞向远处器官转移扩散过程中短暂有利。
