Expression and function of the chemokine receptor CCR7 in thyroid carcinomas
Expression and function of the chemokine receptor CCR7 in thyroid carcinomas
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DOI：
10.1677/joe.1.06688
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发表时间：
2006-10-01
影响因子：
4
通讯作者：
Leite, Valeriano
中科院分区：
文献类型：
--
作者：
Sancho, Margarida;Vieira, Joaquim Miguel;Leite, Valeriano
趋化因子受体 CCR7 在淋巴细胞和树突状细胞流入淋巴结及其内部的运输中发挥着关键作用，而淋巴结是甲状腺乳头状癌 (PTC) 和髓样癌 (MTC) 的首选转移部位。为了确定 CCR7 在介导甲状腺癌转移行为中的可能作用，我们分析了其在不同组织型的正常和肿瘤甲状腺组织中的表达，并研究了 CCR7 配体 CCL21 激活其的体外效应。使用实时定量 PCR，我们观察到 CCR7 在 PTC 和 MTC 中的表达高于滤泡性甲状腺癌和低分化甲状腺癌。与滤泡型 PTC 相比，经典型 PTC 中 CCR7 的表达量高出九倍，并且其在 MTC 中的表达与淋巴结转移显着相关。 CCR7 的免疫组织化学染色显示甲状腺肿瘤细胞中有蛋白表达，在 PTC、MTC 及其淋巴结转移 (LNM) 中表达强度较高。我们进一步表明，CCL21 刺激表达 CCR7 的甲状腺肿瘤细胞系 (TPC-1) 可促进细胞增殖和迁移，并且 CCL21 在这些细胞中的趋化作用涉及肌动蛋白聚合、增加 β1-整合素表达和增加基质金属蛋白酶分泌。综上所述，我们的结果表明，CCL21（一种在淋巴结中大量表达的趋化因子）对甲状腺癌细胞的 CCR7 激活有利于组织侵袭和细胞增殖，因此可能促进甲状腺癌生长和 LNM。
The chemokine receptor CCR7 plays a critical role in lymphocyte and dendritic cell trafficking into and within lymph nodes, the preferential metastatic site for papillary (PTC) and medullary (MTC) thyroid carcinomas. In order to determine a possible role for CCR7 in mediating the metastatic behaviour of thyroid carcinomas, we analysed its expression in normal and tumoral thyroid tissues of different histotypes and studied the in vitro effects of its activation by the CCR7 ligand, CCL21. Using real-time quantitative-PCR, we observed that CCR7 expression was higher in PTCs and MTCs than in follicular and poorly differentiated thyroid carcinomas. CCR7 expression was ninefold higher in classic compared with follicular variants of PTCs, and its expression in MTCs was significantly correlated with lymph node metastases. immunohistochemical staining for CCR7 showed protein expression in neoplastic thyroid cells, with higher intensity in PTCs, MTCs and their lymph node metastases (LNMs). We further showed that CCL21 stimulation of a CCR7-expressing thyroid tumour cell line (TPC-1) promotes cell proliferation and migration, and the chemotactic effect of CCL21 in these cells involves actin polymerization, increased beta 1-integrin expression and increased matrix metalloproteinase secretion. Taken together, our results demonstrate that CCR7 activation on thyroid carcinoma cells by CCL21 - a chemokine abundantly expressed in lymph nodes - favours tissue invasion and cell proliferation, and therefore may promote thyroid carcinoma growth and LNM.