CORRELATION OF VLA-4 INTEGRIN EXPRESSION WITH METASTATIC POTENTIAL IN VARIOUS HUMAN TUMOR-CELL LINES

CORRELATION OF VLA-4 INTEGRIN EXPRESSION WITH METASTATIC POTENTIAL IN VARIOUS HUMAN TUMOR-CELL LINES
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DOI:
10.1111/j.1432-0436.1993.tb00636.x
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发表时间:
1993-03-01
期刊:
影响因子:
2.9
通讯作者:
TARIN, D
TARIN, D
中科院分区:
生物学3区
文献类型:
--
作者:
BAO, L;PIGOTT, R;TARIN, D

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这项研究的重点是最近被认为是用于循环白细胞运输的细胞附着受体的一些分子物种是否在转移的肿瘤细胞群上表达。这已经在活培养的转移和非转移肿瘤细胞系上进行了研究,以及在接种到裸鼠体内后形成的原发肿瘤和转移瘤的冰冻组织切片上进行了研究。在这里,我们报告了我们使用免疫荧光显微镜、荧光激活细胞分析、免疫细胞化学和体内肿瘤行为的病理学研究获得的数据,这些数据表明整合素分子VLA-4的表达与转移过程的执行呈正相关。已知该分子是至少两种配体的受体,即可诱导的内皮细胞黏附分子VCAM-1和细胞外基质成分纤维连接蛋白,并被认为在淋巴细胞的附着和疏导中具有重要的机械作用。目前的发现表明,该分子在转移细胞群体上的表达与非转移细胞群体相比存在差异,支持并推广了其他实验室最近关于转移肿瘤细胞上存在各种白细胞黏附受体的报道。越来越多的证据表明,在肿瘤细胞系中不适当地表达这些表面黏附分子中的一个或多个,可能会赋予受影响克隆的后代一些转移行为所需的特性。到目前为止,不同研究小组收集的全部信息也提供了一些早期线索,表明表达的分子类型可能与肿瘤的组织起源及其转移扩散模式有关。在这一阶段,目前还没有足够的信息来评论迄今为止发现的任何一种白细胞黏附分子的表达是否对转移是必要的。或者它们在肿瘤细胞表面的部署是否只是促进作用。然而,现有的大量信息为研究干扰这些分子物种的功能是否会阻碍或减缓疾病的几何发展提供了强大的动力。
This investigation has focused on whether a number of molecular species, which have recently been recognised as components of cell attachment receptors utilised in recirculatory leukocyte traffic, are expressed on metastatic tumour cell populations. This has been studied on live cultured metastatic and non-metastatic tumour cell lines as well as on histological sections of frozen tissue from primary tumours and metastases which they formed after inoculation into nude mice. Here we report data we have obtained using immunofluorescence microscopy, fluorescence activated cell analysis, immunocytochemistry and pathological investigation of tumour behaviour in vivo, which converge to indicate that expression of the integrin molecule VLA-4 is positively associated with the execution of the metastatic process. This molecule is known to be a receptor for at least two ligands, namely the inducible endothelial adhesion molecule VCAM-1 and the extracellular matrix component fibronectin, and is thought to be mechanistically important in the attachment and diapodesis of lymphocytes. The present findings, indicating differential expression of this molecule on metastatic cell populations relative to non-metastatic cell populations, support and extend recent reports from other laboratories, of the presence of various leukocyte adhesion receptors on metastatic tumour cells. This accumulating evidence suggests that inappropriate expression of one or more of these surface adhesion molecules in tumour cell lineages may endow the progeny of the affected clones with some of the properties needed for metastatic behaviour. The total information so far assembled by various groups also provides some early clues suggesting that the types of molecules expressed may be related to the histogenetic origin of the tumour and its pattern of metastatic spread. At this stage there is insufficient information to comment on whether expression of any of the leukocyte adhesion molecules so far identified is essential for metastasis. or whether their deployment on the tumour cell surface is just facilitatory. However, the body of information now available provides a strong incentive to study whether interference with the functions of such molecular species could impede or reduce the geometric progression of the disease.