Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Shantou University Medical College, PR China; Changjiang Scholar's Laboratory of Shantou University Medical College, PR China.
Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Shantou University Medical College, PR China.
Int Immunopharmacol. 2017 Oct;51:124-130. doi: 10.1016/j.intimp.2017.07.018. Epub 2017 Aug 19.
CCR10, a member of the chemokine receptor subfamily, is overexpressed in several tumors and play a crucial role in cancer development and progression. However, the functions of CCR10 in breast cancer are unknown. Here, we detected the protein levels of CCR10 in breast cancer cells by western blotting, and examined CCR10 expression in breast cancer tissues via immunohistochemical assay. The results showed that CCR10 expression was elevated in breast cancer MCF7, BT-474 and MDA-MB-231 cells. Further, 63 of 89 cases (70.8%) had positive CCR10 staining, and the CCR10 level was closely related to capsular invasion, lymph node metastasis and tumor stage. Moreover, CCL27, the ligand of CCR10, dose-dependently stimulated the invasion and migration of breast cancer cells, and promoted MMP-7 expression and ERK1/2 activation. CCR10 knockdown in breast cancer cells through siRNA transfection attenuated CCL27-induced cell invasiveness, and suppressed MMP-7 expression and ERK1/2 activation. Additionally, blocking the ERK1/2 pathway inhibited the CCL27/CCR10-promoted cell invasion of breast cancer cells. Together, these data suggest that CCL27/CCR10 interaction induces the ERK1/2 pathway, which then increases MMP-7 expresion and subsequently promotes breast cancer cell invasion and migration. Thus, CCR10 may be a key regulator in breast cancer cell invasion and migration.
CCR10 是趋化因子受体亚家族的成员，在几种肿瘤中过表达，并在癌症的发生和发展中发挥关键作用。然而，CCR10 在乳腺癌中的功能尚不清楚。在这里，我们通过 Western blot 检测了乳腺癌细胞中 CCR10 的蛋白水平，并通过免疫组织化学检测了乳腺癌组织中 CCR10 的表达。结果表明，CCR10 在乳腺癌 MCF7、BT-474 和 MDA-MB-231 细胞中表达上调。此外，89 例中有 63 例（70.8%）CCR10 染色阳性，CCR10 水平与包膜浸润、淋巴结转移和肿瘤分期密切相关。此外，CCR10 的配体 CCL27 呈剂量依赖性地刺激乳腺癌细胞的侵袭和迁移，并促进 MMP-7 的表达和 ERK1/2 的激活。通过 siRNA 转染敲低乳腺癌细胞中的 CCR10，减弱了 CCL27 诱导的细胞侵袭，抑制了 MMP-7 的表达和 ERK1/2 的激活。此外，阻断 ERK1/2 通路抑制了 CCL27/CCR10 促进的乳腺癌细胞侵袭。总之，这些数据表明，CCL27/CCR10 相互作用诱导 ERK1/2 通路，从而增加 MMP-7 的表达，进而促进乳腺癌细胞的侵袭和迁移。因此，CCR10 可能是乳腺癌细胞侵袭和迁移的关键调节因子。
