151. Placental supernatants’ enhancement of the metastatic potential of breast cancer cells: is estrogen receptor (ERα) essential for this phenomenon?
- Author
-
Oded Komemi, Liat Drucker, Shelly Tartakover Matalon, Michael Lishner, Michal Avrech Bar, Meir Pomeranz, and Ami Fishman
- Subjects
STAT3 Transcription Factor ,medicine.drug_class ,Placenta ,Estrogen receptor ,Breast Neoplasms ,03 medical and health sciences ,0302 clinical medicine ,Cell Movement ,Pregnancy ,medicine ,Humans ,Progesterone ,Cell Proliferation ,030219 obstetrics & reproductive medicine ,Cell growth ,business.industry ,Cell Cycle ,Estrogen Receptor alpha ,Obstetrics and Gynecology ,Estrogens ,Cell migration ,General Medicine ,Cell cycle ,Pregnancy Trimester, First ,Progesterone Receptor Positive ,medicine.anatomical_structure ,Estrogen ,030220 oncology & carcinogenesis ,MCF-7 Cells ,Cancer research ,Female ,business ,Pregnancy Complications, Neoplastic ,Hormone - Abstract
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.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.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.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.
- Published
- 2019