Role of Lymphatic Endothelium in Vascular Escape of Engineered Human Breast Microtumors

Alex J. Seibel, Owen M. Kelly, Yoseph W. Dance, Celeste M. Nelson, Joe Tien

Research output: Contribution to journalArticlepeer-review


Introduction: Lymphatic vasculature provides a route for metastasis to secondary sites in the body. The role of the lymphatic endothelium in mediating the entry of breast cancer cells into the vasculature remains unclear. Methods: In this study, we formed aggregates of MDA-MB-231 human breast carcinoma cells next to human microvascular lymphatic endothelial cell (LEC)-lined cavities in type I collagen gels to model breast microtumors and lymphatic vessels, respectively. We tracked invasion and escape of breast microtumors into engineered lymphatics or empty cavities under matched flow rates for up to sixteen days. Results: After coming into contact with a lymphatic vessel, tumor cells escape by moving between the endothelium and the collagen wall, between endothelial cells, and/or into the endothelial lumen. Over time, tumor cells replace the LECs within the vessel wall and create regions devoid of endothelium. The presence of lymphatic endothelium slows breast tumor invasion and escape, and addition of LEC-conditioned medium to tumors is sufficient to reproduce nearly all of these inhibitory effects. Conclusions: This work sheds light on the interactions between breast cancer cells and lymphatic endothelium during vascular escape and reveals an inhibitory role for the lymphatic endothelium in breast tumor invasion and escape.

Original languageEnglish (US)
Pages (from-to)553-569
Number of pages17
JournalCellular and Molecular Bioengineering
Issue number6
StatePublished - Dec 2022

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology
  • Modeling and Simulation


  • Intravasation
  • Lymphovascular invasion
  • Microphysiological system
  • Microvascular tissue engineering
  • Mosaic vessel
  • Triple-negative breast cancer
  • Tumor engineering


Dive into the research topics of 'Role of Lymphatic Endothelium in Vascular Escape of Engineered Human Breast Microtumors'. Together they form a unique fingerprint.

Cite this