Hormone-dependent placental manipulation of breast cancer cell migration

G. Epstein Shochet, S. Tartakover Matalon*, L. Drucker, M. Pomeranz, A. Fishman, G. Rashid, V. Oron-Karni, M. Pasmanik-Chor, M. Lishner

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Breast cancer during pregnancy is often more advanced than in non-pregnant women. Nevertheless, no case of metastasis inside the placenta has been reported. Previously, we showed that placental-explants eliminated breast cancer cells from their surroundings, due to cell-death and elevated migration. Our objective was to find the underlying mechanisms of these phenomena. METHODS: AND RESULTSOur model contained Michigan Cancer Foundation 7 (MCF7) or T47D cells co-cultured with and without human placental explants. Microarray analysis, validated by quantitative PCR, of MCF7 following their placental co-culture suggested activation of estrogen (E2) signaling. As extensive cross-talk exists between E2 and progesterone, their involvement in mediating placental effects on breast cancer cells was tested. Indeed, addition of E2 and progesterone receptor (ER and PR) inhibitors to the co-culture system reduced cancer cell motility, yet did not alter cell-cycle or death. E2 and progesterone concentrations in placental media were found to be similar to those of early pregnancy blood levels. Interestingly, placental-breast cancer co-culture media contained lower progesterone (P < 0.05) and higher E2 (200, P < 0.05) levels than placentae cultured separately. Placental supernatant and E2 and progesterone at placental levels were sufficient to increase MCF7 and T47D migration and invasion (P < 0.05), yet did not alter MCF7 cell-cycle or death. Furthermore, placental supernatant elevated p38 and Jun N-terminal kinase (JNK) phosphorylation in both cell lines (P < 0.05). Inhibitors of JNK, ER and PR reversed MCF7 and T47D motility induced by the placenta, suggesting their involvement. CONCLUSIONS: We suggest that E2 and progesterone contribute to cell migration away from placental areas. We hypothesize that they may increase metastatic spread to other organs in pregnancy.

Original languageEnglish
Pages (from-to)73-88
Number of pages16
JournalHuman Reproduction
Volume27
Issue number1
DOIs
StatePublished - Jan 2012

Keywords

  • breast cancer cells
  • motility
  • placenta
  • pregnancy

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