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Article

12(S)-HETE induces lymph endothelial cell retraction in vitro by upregulation of SOX18

  • Authors:
    • Adryan Fristiohady
    • Daniela Milovanovic
    • Sigurd Krieger
    • Nicole Huttary
    • Chi Huu Nguyen
    • Jose Basilio
    • Walter Jäger
    • Rainer De Martin
    • Georg Krupitza
  • View Affiliations / Copyright

    Affiliations: Department of Clinical Pharmacy and Diagnostics, Faculty of Life Sciences, University of Vienna, A-1090 Vienna, Austria, Department of Pathology, Medical University of Vienna, A-1090 Vienna, Austria, Department of Vascular Biology and Thrombosis Research, Centre of Biomolecular Medicine and Pharmacology, Medical University of Vienna, A-1090 Vienna, Austria
  • Pages: 307-316
    |
    Published online on: April 26, 2018
       https://doi.org/10.3892/ijo.2018.4378
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Abstract

Metastasising breast cancer cells communicate with adjacent lymph endothelia, intravasate and disseminate through lymphatic routes, colonise lymph nodes and finally metastasize to distant organs. Thus, understanding and blocking intravasation may attenuate the metastatic cascade at an early step. As a trigger factor, which causes the retraction of lymph endothelial cells (LECs) and opens entry ports for tumour cell intravasation, MDA-MB231 breast cancer cells secrete the pro-metastatic arachidonic acid metabolite, 12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid [12(S)-HETE]. In the current study, treatment of LECs with 12(S)-HETE upregulated the expression of the transcription factors SRY-related HMG-box 18 (SOX18) and prospero homeobox protein 1 (PROX1), which determine endothelial development. Thus, whether they have a role in LEC retraction was determined using a validated intravasation assay, small interfering RNA mediated knockdown of gene expression, and mRNA and protein expression analyses. Specific inhibition of SOX18 or PROX1 significantly attenuated in vitro intravasation of MDA-MB231 spheroids through the LEC barrier and 12(S)-HETE-triggered signals were transduced by the high and low affinity receptors, 12(S)-HETE receptor and leukotriene B4 receptor 2. In addition, the current findings indicate that there is crosstalk between SOX18 and nuclear factor κ-light-chain-enhancer of activated B cells, which was demonstrated to contribute to MDA-MB231/lymph endothelial intravasation. The present data demonstrate that the endothelial-specific and lymph endothelial-specific transcription factors SOX18 and PROX1 contribute to LEC retraction.
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Copy and paste a formatted citation
Spandidos Publications style
Fristiohady A, Milovanovic D, Krieger S, Huttary N, Nguyen CH, Basilio J, Jäger W, De Martin R and Krupitza G: 12(S)-HETE induces lymph endothelial cell retraction in vitro by upregulation of SOX18. Int J Oncol 53: 307-316, 2018.
APA
Fristiohady, A., Milovanovic, D., Krieger, S., Huttary, N., Nguyen, C.H., Basilio, J. ... Krupitza, G. (2018). 12(S)-HETE induces lymph endothelial cell retraction in vitro by upregulation of SOX18. International Journal of Oncology, 53, 307-316. https://doi.org/10.3892/ijo.2018.4378
MLA
Fristiohady, A., Milovanovic, D., Krieger, S., Huttary, N., Nguyen, C. H., Basilio, J., Jäger, W., De Martin, R., Krupitza, G."12(S)-HETE induces lymph endothelial cell retraction in vitro by upregulation of SOX18". International Journal of Oncology 53.1 (2018): 307-316.
Chicago
Fristiohady, A., Milovanovic, D., Krieger, S., Huttary, N., Nguyen, C. H., Basilio, J., Jäger, W., De Martin, R., Krupitza, G."12(S)-HETE induces lymph endothelial cell retraction in vitro by upregulation of SOX18". International Journal of Oncology 53, no. 1 (2018): 307-316. https://doi.org/10.3892/ijo.2018.4378
Copy and paste a formatted citation
x
Spandidos Publications style
Fristiohady A, Milovanovic D, Krieger S, Huttary N, Nguyen CH, Basilio J, Jäger W, De Martin R and Krupitza G: 12(S)-HETE induces lymph endothelial cell retraction in vitro by upregulation of SOX18. Int J Oncol 53: 307-316, 2018.
APA
Fristiohady, A., Milovanovic, D., Krieger, S., Huttary, N., Nguyen, C.H., Basilio, J. ... Krupitza, G. (2018). 12(S)-HETE induces lymph endothelial cell retraction in vitro by upregulation of SOX18. International Journal of Oncology, 53, 307-316. https://doi.org/10.3892/ijo.2018.4378
MLA
Fristiohady, A., Milovanovic, D., Krieger, S., Huttary, N., Nguyen, C. H., Basilio, J., Jäger, W., De Martin, R., Krupitza, G."12(S)-HETE induces lymph endothelial cell retraction in vitro by upregulation of SOX18". International Journal of Oncology 53.1 (2018): 307-316.
Chicago
Fristiohady, A., Milovanovic, D., Krieger, S., Huttary, N., Nguyen, C. H., Basilio, J., Jäger, W., De Martin, R., Krupitza, G."12(S)-HETE induces lymph endothelial cell retraction in vitro by upregulation of SOX18". International Journal of Oncology 53, no. 1 (2018): 307-316. https://doi.org/10.3892/ijo.2018.4378
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