Laboratoire de Radiobiologie et Oncologie, CEA, Fontenay-aux-Roses, France.
Clin Lung Cancer. 2010 May;11(3):187-91. doi: 10.3816/CLC.2010.n.024.
Recent studies suggest that chemokines are involved in organ-specific metastatic relapse. We evaluated the potential implications of chemokine receptors in the development of adrenal metastasis after complete resections of primary non-small-cell lung cancer.
We studied a unique cohort of 21 primary lung cancers with matched adrenal metastases for the expression of CX3CR1, CXCR4, CCR6, and CCR7, using immunohistochemistry.
Although CXCR4, CX3CR1, and CCR7 were independently expressed in primary and corresponding metastases, CCR6 was clearly overexpressed in adrenal metastases, compared with corresponding primary tumors. Moreover, CCL20, the ligand of CCR6, was preferentially expressed in adrenal tissues that developed metastases.
We report for the first time (to the best of our knowledge) a potential role for the CCR6 receptor in the organ orientation of the development of metastases in lung cancer. We demonstrated a statistically significant overexpression of CCR6 in adrenal metastases compared with primary lung tumors, indicating that the increased production of CCL20 in adrenal glands might contribute to the selective recruitment of CCR6-expressing cancer cells in lung cancer. This study, in concordance with the data obtained in animal models, suggests that the chemokine receptor family constitutes a biologic support of the "seed and soil" theory.
最近的研究表明趋化因子参与了器官特异性转移复发。我们评估了趋化因子受体在原发性非小细胞肺癌完全切除后肾上腺转移发展中的潜在作用。
我们使用免疫组织化学法研究了 21 例原发性肺癌和匹配的肾上腺转移瘤的独特队列，以评估 CX3CR1、CXCR4、CCR6 和 CCR7 的表达。
尽管 CXCR4、CX3CR1 和 CCR7 在原发性肿瘤和相应转移瘤中独立表达，但 CCR6 在肾上腺转移瘤中明显过表达，与相应的原发性肿瘤相比。此外，CCL20 是 CCR6 的配体，在发生转移的肾上腺组织中优先表达。
我们首次（据我们所知）报告了 CCR6 受体在肺癌转移器官定向发展中的潜在作用。我们发现在肾上腺转移瘤中 CCR6 的表达明显高于原发性肺肿瘤，表明在肾上腺中 CCL20 的产生增加可能有助于选择性招募表达 CCR6 的肺癌细胞。这项研究与动物模型中获得的数据一致，表明趋化因子受体家族构成了“种子和土壤”理论的生物学支持。
