Autologous Chemotaxis as a Mechanism of Tumor Cell Homing to Lymphatics via Interstitial Flow and Autocrine CCR7 Signaling

Jacqueline D. Shields, Mark E. Fleury, Carolyn Yong, Alice Tomei, Gwendalyn J. Randolph, Melody A. Swartz

Research output: Contribution to journalArticle

308 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)526-538
Number of pages13
JournalCancer Cell
Volume11
Issue number6
DOIs
StatePublished - Jun 12 2007
Externally publishedYes

Fingerprint

Autocrine Communication
Chemotaxis
Neoplasms
Cell Movement
Lymphatic Endothelium
Lymphatic Metastasis
Drainage
Lymph Nodes
Neoplasm Metastasis
Ligands
Cell Line

Keywords

  • CELLBIO

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Autologous Chemotaxis as a Mechanism of Tumor Cell Homing to Lymphatics via Interstitial Flow and Autocrine CCR7 Signaling. / Shields, Jacqueline D.; Fleury, Mark E.; Yong, Carolyn; Tomei, Alice; Randolph, Gwendalyn J.; Swartz, Melody A.

In: Cancer Cell, Vol. 11, No. 6, 12.06.2007, p. 526-538.

Research output: Contribution to journalArticle

Shields, Jacqueline D. ; Fleury, Mark E. ; Yong, Carolyn ; Tomei, Alice ; Randolph, Gwendalyn J. ; Swartz, Melody A. / Autologous Chemotaxis as a Mechanism of Tumor Cell Homing to Lymphatics via Interstitial Flow and Autocrine CCR7 Signaling. In: Cancer Cell. 2007 ; Vol. 11, No. 6. pp. 526-538.
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