Role of ICAM1 in invasion of human breast cancer cells
Role of ICAM1 in invasion of human breast cancer cells
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DOI：
10.1093/carcin/bgi070
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发表时间：
2005-05-01
期刊：
影响因子：
4.7
通讯作者：
Denissenko, MF
中科院分区：
文献类型：
--
作者：
Rosette, C;Roth, RB;Denissenko, MF
我们先前确定了染色体19p13.2上的一个区域，该区域跨越编码细胞间粘附分子（ICAM）、ICAM 1、ICAM 4和ICAM 5的基因作为乳腺癌易感基因座。该区域的遗传变异也与疾病严重程度的指标相关，包括向其他器官转移的更高比率。基于这种关联，我们着手探讨ICAM 1在人乳腺癌细胞增殖和侵袭中的作用。我们观察到ICAM 1在mRNA和蛋白水平的下调导致了通过基质胶基质对人乳腺细胞侵袭的强烈抑制。在相同条件下，对体外细胞增殖无明显影响。细胞与抗ICAM 1的抗体孵育以剂量依赖性方式阻断了高转移性MDA-MB-435细胞系的侵袭，而不影响细胞迁移。我们还表明，细胞表面的ICAM 1蛋白表达水平与5个人乳腺癌细胞系的转移潜能呈正相关，并且与邻近正常组织相比，乳腺肿瘤中ICAM 1 mRNA水平升高。这些结果证实了我们先前的遗传发现，即ICAM区域的变异与转移的发生有关，并建立了ICAM 1在转移性人乳腺癌细胞系侵袭中的因果作用。
We identified previously a region on chromosome 19p13.2 spanning the genes encoding the intercellular adhesion molecules (ICAM), ICAM1, ICAM4 and ICAM5 as a breast cancer susceptibility locus. Genetic variants in this region were also associated with indicators of disease severity, including higher rates of metastases to other organs. Based on this association, we set out to explore the role of ICAM1 in proliferation and invasion of human breast cancer cells. We observed that ICAM1 downregulation at the mRNA and protein levels led to a strong suppression of human breast cell invasion through a matrigel matrix. Under the same conditions, no significant effect on cell proliferation in vitro was seen. Incubation of cells with an antibody against ICAM1 blocked invasion of the highly metastatic MDA-MB-435 cell line in a dose-dependent manner without affecting cell migration. We also demonstrated that the level of ICAM1 protein expression on the cell surface positively correlated with metastatic potential of five human breast cancer cell lines and that ICAM1 mRNA levels were elevated in breast tumor compared with adjacent normal tissue. These results corroborate our previous genetic finding that variations in the ICAM region are associated with the occurrence of metastases and establish a causal role of ICAM1 in invasion of metastatic human breast carcinoma cell lines.