NF-κB mediates the 12(S)-HETE-induced endothelial to mesenchymal transition of lymphendothelial cells during the intravasation of breast carcinoma cells
2011

How Breast Cancer Cells Invade Lymphatic Vessels

publication Evidence: moderate

Author Information

Author(s): Vonach C, Viola K, Giessrigl B, Huttary N, Raab I, Kalt R, Krieger S, Vo T P N, Madlener S, Bauer S, Marian B, Hämmerle M, Kretschy N, Teichmann M, Hantusch B, Stary S, Unger C, Seelinger M, Eger A, Mader R, Jäger W, Schmidt W, Grusch M, Dolznig H, Mikulits W, Krupitza G

Primary Institution: Medical University of Vienna

Hypothesis

12(S)-HETE triggers endothelial to mesenchymal transition.

Conclusion

The study shows that 12(S)-HETE-induced intravasation of breast cancer cells through lymphendothelial cells requires an NF-κB-dependent process.

Supporting Evidence

  • 12(S)-HETE induces pro-metastatic protein expression patterns in lymphendothelial cells.
  • NF-κB inhibition reduced the formation of circular chemorepellent-induced defects (CCID) by 50%.
  • ZEB1 knockdown abrogated 12(S)-HETE-mediated VE-cadherin repression.

Takeaway

Breast cancer cells can make holes in the walls of lymphatic vessels to spread, and a special substance called 12(S)-HETE helps them do this by changing the cells' behavior.

Methodology

A 3D co-culture model was developed using MCF-7 breast cancer cell spheroids and human lymphendothelial cell monolayers to study the effects of 12(S)-HETE.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1038/bjc.2011.194

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