Placental supernatants’ enhancement of the metastatic potential of breast cancer cells: is estrogen receptor (ERα) essential for this phenomenon?
Purpose Pregnancy-associated breast cancer (PABC) is usually diagnosed at an advanced stage in comparison to non-pregnant women. The placenta secretes hormones and cytokines, which affect breast cancer progression. Previously, we demonstrated that human placental secretome facilitates the survival a...
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Published in | Archives of gynecology and obstetrics Vol. 300; no. 4; pp. 981 - 991 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Berlin/Heidelberg
Springer Berlin Heidelberg
01.10.2019
Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | Purpose
Pregnancy-associated breast cancer (PABC) is usually diagnosed at an advanced stage in comparison to non-pregnant women. The placenta secretes hormones and cytokines, which affect breast cancer progression. Previously, we demonstrated that human placental secretome facilitates the survival and migration of ERα+ breast cancer cells (BCCL), but pregnant women have a relatively high frequency of ERα-negative tumors. In the current study, we analyzed the effect of placental secretome on ERα-negative BCCL.
Methods
BCCL [MCF-7(estrogen/progesterone receptor positive (ERα+/PR+), ERα reduced MCF-7 (siRNA, MCF-7 ERα−), HS-578 and BT-549 cells (both ER−/PR−)] were exposed to supernatants (collected from first trimester human placental explants and from control BCCL) or to E2 + P4 (estrogen + progesterone) in placental supernatant concentrations and then tested for cell proliferation (number, cell cycle, PCNA), cell-death, cell migration, STAT3 pathway activation and functionality.
Results
Silencing ERα in the MCF-7 cells negated the placental supernatant and E2 + P4 enhancement of cell migration (> 130%,
p
< 0.05), number (> 120%) and survival (~ 130%). However, it had no such effect on MCF-7-ER− migration, which was still elevated in the presence of placental secretome. ER−/PR− BCCL were unaffected by the hormones, but placental secretome significantly elevated their migration (115%), number (140–170%), STAT3 phosphorylation (~ 180%) and BT-549 STAT3 level. These effects were negated by the STAT3 inhibitor.
Conclusions
Placental supernatant facilitates BCCL malignant characteristics by activating ERα in estrogen responsive cells and STAT3 in ERα- BCCL. This indicates a possible mechanism that may underlie PABC’s advanced state and suggests STAT3 pathway as a therapeutic target for PABC. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0932-0067 1432-0711 |
DOI: | 10.1007/s00404-019-05243-4 |