TY - JOUR
T1 - Placenta-breast cancer cell interactions promote cancer cell epithelial mesenchymal transition via TGFβ/JNK pathway
AU - Epstein Shochet, Gali
AU - Tartakover-Matalon, Shelly
AU - Drucker, Liat
AU - Pasmanik-Chor, Metsada
AU - Pomeranz, Meir
AU - Fishman, Ami
AU - Lishner, Michael
N1 - Publisher Copyright:
© 2014, Springer Science+Business Media Dordrecht.
PY - 2014/12/5
Y1 - 2014/12/5
N2 - 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.
AB - 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.
KW - Breast cancer
KW - EMT
KW - Migration
KW - Placenta
KW - Pregnancy
UR - http://www.scopus.com/inward/record.url?scp=84916896382&partnerID=8YFLogxK
U2 - 10.1007/s10585-014-9683-0
DO - 10.1007/s10585-014-9683-0
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C2 - 25316285
AN - SCOPUS:84916896382
SN - 0262-0898
VL - 31
SP - 961
EP - 975
JO - Clinical and Experimental Metastasis
JF - Clinical and Experimental Metastasis
IS - 8
ER -