CCR7 mediates directed growth of melanomas towards lymphatics.
CCR7 mediates directed growth of melanomas towards lymphatics.
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DOI：
10.1111/j.1549-8719.2010.00074.x
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发表时间：
2011-04
期刊：
影响因子：
--
通讯作者：
Bates DO
中科院分区：
文献类型：
--
作者：
Emmett MS;Lanati S;Dunn DB;Stone OA;Bates DO
为了确定趋化转移，黑色素瘤向高淋巴密度区域的优先生长，是否在体内依赖于CCL 21/CCR 7。淋巴管内皮细胞（LECs）产生趋化因子CCL 21。转移性黑色素瘤细胞表达CCR 7，其受体，并表现出趋化性转移，由此转移性细胞识别并向淋巴密度较高的区域生长。我们使用了两种体内模型的定向生长向仓库的LEC的黑色素瘤细胞过度表达CCR 7。通过活体荧光显微镜跟踪注射的LEC，通过生物发光跟踪黑色素瘤生长。趋化因子受体CCR 7的过表达使得非转移性肿瘤细胞能够识别并向LEC生长（与对照相比为3.9倍），但在没有增加的淋巴清除的情况下，在体外和体内不能识别并向血液内皮细胞生长（0.9倍）。趋化性转移被CCL 21中和抗体抑制（对照的4-17%）。此外，小鼠B16黑色素瘤中的CCR 7表达导致体内转运转移（50-100%的小鼠），这在体内对照肿瘤（0-50%）中不太常见。这些结果表明，识别LEC的肿瘤表达淋巴特异性配体的受体，有助于识别和黑色素瘤细胞的侵袭，并提供了进一步的证据，肿瘤扩散的趋化转移模型。
To determine whether chemotactic-metastasis, the preferential growth of melanomas towards areas of high lymphatic density, is CCL21/CCR7 dependent in vivo. Lymphatic endothelial cells (LECs) produce the chemokine CCL21. Metastatic melanoma cells express CCR7, its receptor, and exhibit chemotactic-metastasis, whereby metastatic cells recognise and grow towards areas of higher lymphatic density. We used two in vivo models of directional growth towards depots of LECs of melanoma cells over-expressing CCR7. Injected LEC were tracked by intravital fluorescence microscopy, and melanoma growth by bioluminescence. Over-expression of the chemokine receptor CCR7 enables non-metastatic tumour cells to recognise and grow towards LECs (3.9 fold compared with control), but not blood endothelial cells (0.9 fold) in vitro and in vivo, in the absence of increased lymphatic clearance. Chemotactic metastasis was inhibited by a CCL21 neutralising antibody (4-17% of control). Furthermore, CCR7 expression in mouse B16 melanomas resulted in in-transit metastasis (50-100% of mice) that was less often seen with control tumours (0-50%) in vivo. These results suggest that recognition of LEC by tumours expressing receptors for lymphatic specific ligands contributes towards the identification and invasion of lymphatics by melanoma cells, and provides further evidence for a chemotactic metastasis model of tumour spread.
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