Involvement of chemokine receptors in breast cancer metastasis
Involvement of chemokine receptors in breast cancer metastasis
复制标题
DOI：
10.1038/35065016
复制
发表时间：
2001-03-01
期刊：
影响因子：
64.8
通讯作者：
Zlotnik, A
中科院分区：
文献类型：
--
作者：
Müller, A;Homey, B;Zlotnik, A
乳腺癌的特点是区域淋巴结、骨髓、肺和肝脏有明显的转移模式。肿瘤细胞的迁移和转移与白细胞的转运有许多相似之处，白细胞的转运受到趋化因子及其受体的关键调控。在此，我们报道了趋化因子受体CXCR4和CCR7在人乳腺癌细胞、恶性乳腺肿瘤和转移瘤中的高表达。它们各自的配体CXCL12/SDF-1α和CCL21/6Ckine在代表乳腺癌转移的第一个目的地的器官中表达水平达到峰值。在乳腺癌细胞中，通过CXCR4或CCR7的信号介导肌动蛋白聚合和伪足形成，随后诱导趋化和侵袭性反应。在体内，中和CXCL12/CXCR4的相互作用显著降低乳腺癌细胞向区域淋巴结和肺的转移。恶性黑色素瘤的转移模式与乳腺癌相似，但皮肤转移的发生率也很高，除了CXCR4和CCR7外，还有CCR10的高表达。我们的发现表明，趋化因子及其受体在决定肿瘤细胞转移目的地方面起着关键作用。
Breast cancer is characterized by a distinct metastatic pattern involving the regional lymph nodes, bone marrow, lung and liver. Tumour cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases. Their respective ligands CXCL12/SDF-1 alpha and CCL21/6Ckine exhibit peak levels of expression in organs representing the first destinations of breast cancer metastasis. In breast cancer cells, signalling through CXCR4 or CCR7 mediates actin polymerization and pseudopodia formation, and subsequently induces chemotactic and invasive responses. In vivo, neutralizing the interactions of CXCL12/CXCR4 significantly impairs metastasis of breast cancer cells to regional lymph nodes and lung. Malignant melanoma, which has a similar metastatic pattern as breast cancer but also a high incidence of skin metastases, shows high expression levels of CCR10 in addition to CXCR4 and CCR7. Our findings indicate that chemokines and their receptors have a critical role in determining the metastatic destination of tumour cells.