Sutherland A, Mirjolet J-F, Maho A, Parmentier M
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, Université Libre de Bruxelles, Brussels, Belgium.
Cancer Gene Ther. 2007 Oct;14(10):847-57. doi: 10.1038/sj.cgt.7701074. Epub 2007 Jun 29.
Chemokines and their receptors play important roles in various aspects of tumoral processes, and evidence was provided for their critical involvement in determining the metastatic destination of tumor cells. Here, we analyzed in vitro and in vivo, how CCR6 expression could alter the behavior of Lewis lung carcinoma (LLC) cells, which were shown to express low levels of the CCR6 ligand, CCL20 (LARC), both in vitro and in vivo. The expression of CCR6 significantly decreased the number of metastases in immunocompetent C57BL/6 mice, without affecting the tumor-forming ability of LLC cells. This was correlated with a decrease in clonogenicity in soft and hard agar, and with increased adhesion to type-IV collagen. These two observations made in basal conditions were enhanced when CCL20 was added to the assay medium. Thus, expression of CCR6 in tumor cells, associated with the local production of CCL20, decreased the metastatic potential of the LLC line. We propose a model, in which the expression of a chemokine receptor in tumor cells can act as a metastasis-suppressor, or a metastasis-promoting factor, according to the expression, or the absence of expression of the cognate ligand(s) in the tumor.
趋化因子及其受体在肿瘤发生发展的各个方面发挥着重要作用，并且有证据表明它们在决定肿瘤细胞转移目的地方面起着关键作用。在此，我们在体外和体内分析了CCR6的表达如何改变Lewis肺癌（LLC）细胞的行为，LLC细胞在体外和体内均显示出低水平表达CCR6配体CCL20（LARC）。CCR6的表达显著减少了免疫健全的C57BL/6小鼠中的转移灶数量，而不影响LLC细胞的成瘤能力。这与软琼脂和硬琼脂中克隆形成能力的降低以及与IV型胶原黏附性的增加相关。当向测定培养基中添加CCL20时，在基础条件下观察到的这两个现象得到增强。因此，肿瘤细胞中CCR6的表达与CCL20的局部产生相关，降低了LLC细胞系的转移潜能。我们提出了一个模型，其中肿瘤细胞中趋化因子受体的表达可根据肿瘤中同源配体的表达或不表达情况，作为转移抑制因子或转移促进因子发挥作用。
