Autologous chemotaxis as a mechanism of tumor cell homing to lymphatics via interstitial flow and autocrine CCR7 signaling.
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.
Shields
Jacqueline D
JD
Institute of Bioengineering, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne 1015, Switzerland.
Fleury
Mark E
ME
Yong
Carolyn
C
Tomei
Alice A
AA
Randolph
Gwendalyn J
GJ
Swartz
Melody A
MA
D019898:Autocrine Communication; D045744:Cell Line, Tumor; D002633:Chemotaxis; D042783:Endothelial Cells / Q000502:physiology; D006801:Humans; D008207:Lymphatic Metastasis; D008208:Lymphatic System / Q000166:cytology* / Q000502:physiology; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism*
C515370:CCR7 protein, human; D054400:Receptors, CCR7; D019707:Receptors, Chemokine