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Placenta-breast cancer cell interactions promote cancer cell epithelial mesenchymal transition via TGFβ/JNK pathway

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Abstract

Women diagnosed with pregnancy associated breast cancer often have advanced cancer with metastases and reduced expression of ERα compared to non-pregnant women. Nevertheless, metastases to the placenta are uncommon. Previously, we demonstrated that breast cancer cells (MCF-7/T47D) migrated from ex vivo human placental explant implantation sites. We aimed to analyze the effect of factors produced during placental implantation or as a result of the interaction between the implanted placentae to cancer cells on cancer cells migration and aggressiveness. We collected supernatants from implanted placentae and placental-breast cancer cells cocultures and analyzed their effects on cancer cells phenotype and pathways. Supernatants collected from breast cancer cells served as controls. We found that supernatants collected from implanted placentae induced modest cancer cells migration that was not accompanied by epithelial to mesenchymal transition (EMT), supported breast cancer cells survival and elevated MCF-7 cell number. The coculture supernatant induced excessive motility and EMT of the MCF-7 cells. This EMT was mediated by Smad3 and JNK/ERK activation. Both placenta and coculture supernatants reduced ERα expression in the cancer cells. Finally, we showed that MCF-7 cocultured with the human placental explants underwent continuous activation of JNK and Smad3 pathways and the EMT process, which led to their migration away from the placental implantation sites. These findings may explain the reduced ERα and elevated metastases found in breast cancer during pregnancy and highlights pathways involved in it.

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Acknowledgments

This work constitutes a section of the PhD thesis of Epstein Shochet Gali, Sackler Faculty of Medicine, Tel-Aviv University, Israel. This work was supported by the ‘Dr Leo Mintz Foundation’ of the Sackler Faculty of Medicine, Tel Aviv University, Israel.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Oncogenetic Laboratory, Meir Medical Center, 45 Tschernchovski St., Kfar Saba, 44281, Israel

    Gali Epstein Shochet, Shelly Tartakover-Matalon, Liat Drucker & Michael Lishner

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Gali Epstein Shochet, Shelly Tartakover-Matalon, Liat Drucker, Meir Pomeranz, Ami Fishman & Michael Lishner

  3. Department of Obstetrics & Gynecology, Meir Medical Center, Kfar Saba, Israel

    Meir Pomeranz & Ami Fishman

  4. Bioinformatics Unit, Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel

    Metsada Pasmanik-Chor

  5. Department of Internal Medicine A, Meir Medical Center, Kfar Saba, Israel

    Michael Lishner

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  1. Gali Epstein Shochet
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  2. Shelly Tartakover-Matalon
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  3. Liat Drucker
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  7. Michael Lishner
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Correspondence to Shelly Tartakover-Matalon.

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Gali Epstein Shochet and Shelly Tartakover Matalon equal contribution.

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Epstein Shochet, G., Tartakover-Matalon, S., Drucker, L. et al. Placenta-breast cancer cell interactions promote cancer cell epithelial mesenchymal transition via TGFβ/JNK pathway. Clin Exp Metastasis 31, 961–975 (2014). https://doi.org/10.1007/s10585-014-9683-0

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  • DOI: https://doi.org/10.1007/s10585-014-9683-0

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