BACKGROUND<\/p>\n
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.<\/p>\n
METHODS AND RESULTS<\/p>\n
Our 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<\/SUB>) signaling. As extensive cross-talk exists between E2<\/SUB> and progesterone, their involvement in mediating placental effects on breast cancer cells was tested. Indeed, addition of E2<\/SUB> 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<\/SUB> 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<\/I> < 0.05) and higher E2<\/SUB> (200%, P<\/I> < 0.05) levels than placentae cultured separately. Placental supernatant and E2<\/SUB> and progesterone at placental levels were sufficient to increase MCF7 and T47D migration and invasion (P<\/I> < 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<\/I> < 0.05). Inhibitors of JNK, ER and PR reversed MCF7 and T47D motility induced by the placenta, suggesting their involvement.<\/p>\n CONCLUSIONS<\/p>\n We suggest that E2<\/SUB> and progesterone contribute to cell migration away from placental areas. We hypothesize that they may increase metastatic spread to other organs in pregnancy.<\/p>\n Source: 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 … Continue reading
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