Shields Jacqueline D, Fleury Mark E, Yong Carolyn, Tomei Alice A, Randolph Gwendalyn J, Swartz Melody A
Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
Cancer Cell. 2007 Jun;11(6):526-38. doi: 10.1016/j.ccr.2007.04.020.
CCR7 is implicated in lymph node metastasis of cancer, but its role is obscure. We report a mechanism explaining how interstitial flow caused by lymphatic drainage directs tumor cell migration by autocrine CCR7 signaling. Under static conditions, lymphatic endothelium induced CCR7-dependent chemotaxis of tumor cells through 3D matrices. However, interstitial flow induced strong increases in tumor cell migration that were also CCR7 dependent, but lymphatic independent. This autologous chemotaxis correlated with metastatic potential in four cell lines and was verified by visualizing directional polarization of cells in the flow direction. Computational modeling revealed that transcellular gradients of CCR7 ligand were created under flow to drive this response. This illustrates how tumor cells may be guided to lymphatics during metastasis.
CCR7与癌症的淋巴结转移有关，但其作用尚不清楚。我们报告了一种机制，解释了由淋巴引流引起的间质流如何通过自分泌CCR7信号传导引导肿瘤细胞迁移。在静态条件下，淋巴管内皮通过三维基质诱导肿瘤细胞的CCR7依赖性趋化作用。然而，间质流导致肿瘤细胞迁移显著增加，这也是CCR7依赖性的，但与淋巴管无关。这种自体趋化作用与四种细胞系的转移潜能相关，并通过观察细胞在流动方向上的定向极化得到证实。计算模型显示，在流动条件下会产生CCR7配体的跨细胞梯度以驱动这种反应。这说明了肿瘤细胞在转移过程中可能是如何被引导至淋巴管的。
