癌细胞伪装成“白细胞”实施癌症扩散

  淋巴结肿胀往往是癌症发生转移扩散的早期征兆，如今来自瑞典卡若琳斯卡学院的研究人员在国际杂志Oncogene上刊登了其最新的研究成果，文章中研究者揭示了癌细胞如何通过伪装成白细胞来隐秘地潜入淋巴系统，相关研究为新型药物的开发提供了帮助和希望。
  人们死于癌症的主要原因往往是因为癌细胞已经扩散形成了子代肿瘤或者发生了转移，而癌细胞通常的扩散路径就是通过淋巴系统来进行，进入淋巴管后癌细胞会迁移到附近的淋巴结，随后膨胀，通过血液进入到其它器官中，然而目前研究者尚不清楚癌细胞利用淋巴细胞进行扩散的机制和原因。
  Jonas Fuxe教授表示，我们并不清楚是否存在特殊的信号来控制癌细胞的扩散，然而近年来有研究证实，炎性是促进癌症转移的主要推动剂，因此抗炎性药物或许也可以在一定程度上抑制癌症的扩散；文章中研究者发现，名为TGF-β的炎性因子可以通过向癌细胞表面补给一种特殊受体来赋予其免疫细胞的特性，这种受体通常存在于白细胞中，而白细胞则可以在淋巴系统中来回穿梭。
  当癌细胞“装备”上特殊受体后，其就会识别并且向淋巴管分泌的梯度物质方向进行移动，并且结合受体，以这种方式癌细胞就可以有效地靶向作用淋巴管并且迁移至淋巴结中，这种方式同免疫细胞的方式类似；因此揭示炎性和癌症之间的关联或许可以为开发抑制癌症的新型疗法提供思路和帮助。
  最后研究者指出，基于以上研究我们后期将会通过大量研究来揭示癌细胞是否会具有其它的免疫细胞特性来进行转移和扩散，如果在这方面有所发现的话，那么研究者或许就可以开发出抑制及减缓癌细胞通过淋巴系统扩散的方法，或可有效降低癌症转移至其它器官的风险。

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转化医学网推荐的原文摘要：

TGF-β1-induced EMT promotes targeted migration of breast cancer cells through the lymphatic system by the activation of CCR7/CCL21-mediated chemotaxis
Oncogene doi:10.1038/onc.2015.133
M-F Pang1,2, A-M Georgoudaki3, L Lambut1, J Johansson1, V Tabor1, K Hagikura1,4, Y Jin1, M Jansson5, J S Alexander6, C M Nelson2, L Jakobsson1, C Betsholtz1, M Sund5, M C I Karlsson3 and J Fuxe1
Tumor cells frequently disseminate through the lymphatic system during metastatic spread of breast cancer and many other types of cancer. Yet it is not clear how tumor cells make their way into the lymphatic system and how they choose between lymphatic and blood vessels for migration. Here we report that mammary tumor cells undergoing epithelial–mesenchymal transition (EMT) in response to transforming growth factor-β (TGF-β1) become activated for targeted migration through the lymphatic system, similar to dendritic cells (DCs) during inflammation. EMT cells preferentially migrated toward lymphatic vessels compared with blood vessels, both in vivo and in 3D cultures. A mechanism of this targeted migration was traced to the capacity of TGF-β1 to promote CCR7/CCL21-mediated crosstalk between tumor cells and lymphatic endothelial cells. On one hand, TGF-β1 promoted CCR7 expression in EMT cells through p38 MAP kinase-mediated activation of the JunB transcription factor. Blockade of CCR7, or treatment with a p38 MAP kinase inhibitor, reduced lymphatic dissemination of EMT cells in syngeneic mice. On the other hand, TGF-β1 promoted CCL21 expression in lymphatic endothelial cells. CCL21 acted in a paracrine fashion to mediate chemotactic migration of EMT cells toward lymphatic endothelial cells. The results identify TGF-β1-induced EMT as a mechanism, which activates tumor cells for targeted, DC-like migration through the lymphatic system. Furthermore, it suggests that p38 MAP kinase inhibition may be a useful strategy to inhibit EMT and lymphogenic spread of tumor cells.