The experimental study of specific COX-2 inhibitors applied to non-surgical therapy of postoperative recurrences and distant metastasis of lung cancer.

虽然已经进行了大量的研究，产生了大量关于转移过程的信息，但对于癌细胞如何传播到远处转移以及将靶分子应用于术后复发和远处转移的非手术治疗方面知之甚少。由于缺乏合适的实验模型系统，对肺癌细胞远距离扩散起关键作用的分子的识别一直受到阻碍。我们最近成功地建立了一个高转移性的人肺癌细胞系NCI-H460-LNM35(以下简称LNM35)，该细胞系不仅可以通过血液途径转移，而且可以通过淋巴途径转移，其发生率为100%。在本研究中，我们发现环氧合酶-2(COX-2)的表达水平与LNM35细胞的体外运动和侵袭能力以及体内转移能力都有很好的相关性，而特异性的COX-2抑制剂首次被证明可以减少肺癌的体内转移。因此，本研究强化了我们先前提出的COX-2可能在肺癌转移过程中发挥作用的概念，并提示了特异性COX-2抑制剂在肺癌治疗中的潜在临床用途。此外，表达谱分析显示，虽然已知COX-2本身在炎症中是可诱导的，但在LNM35中存在各种促炎细胞因子和血管生成趋化趋化因子的上调。这提示肺癌细胞在转移过程中可能模仿炎性细胞。

Although a large number of studies have been conducted, yielding considerable information about the metastatic processes, very little is known about how cancer cells propagate distantmetastasis and about target molecules applied to non-surgical therapy of postoperative recurrences and distant metastasis. Identification of molecules with a crucial role in the distant spread of lungcancer cells has been hampered by scarcity of an appropriate experimental model system. We recently reported the successful establishment of a highly metastatic human lung cancer cell line, NCI-H460-LNM35 (hereafter referred to as LNM35), which is capable of spontaneous metastases not only via hematogenous but also lymphogenous routes with a 100% incidence. In the present study, we found that cyclooxygenase 2 (COX-2) expression llevels correlated well with the capabilities of LNM35 for not only in vitro motility and invasion but also in vivo metastasis, while specific COX-2 inhibitors were shown for the first time to reduce lung cancer metastasis in vivo. The present study thus strengthens our previously stated concept that COX-2 may play a role in the metastatic processes of lung cancers and suggests the potentially clinical usefulness of specific COX-2 inhibitors for the treatment of lung cancer cases. Further, expression-profiling analysisrevealed that, while COX-2 itself is known to be inducible in inflammation, up-regulation of various proinflammatory cytokines and angiogenic chemotactic chemokines was present in LNM35. This suggest that lung cancer cells may mimic inflammatory cells in the process of metastasis.