Breast cancer characteristics are modified by first trimester human placenta: in vitro co-culture study.
BACKGROUND
Pregnant women with breast cancer present with a more advanced disease compared with non-pregnant women. Nevertheless, breast cancer metastasis to the placenta is rare. Trophoblast/tumor implantations share the same biochemical mediators, while only the first is stringently controlled. We hypothesized that the same mechanisms that affect/restrain placental implantation may inhibit metastatic growth in the placenta. We aimed to analyze the effects of human placenta on breast cancer cells.


METHODS
First trimester human placental explants were co-cultured with MCF-7/T47D-eGFP tagged cells. Following culture, placenta/cancer cells/both were fixed, paraffin embedded and sliced for immunohistochemical analysis or sorted by their eGFP expression for future analysis. The tested parameters were: proliferation (immunohistochemistry)/cell cycle (FACS), apoptosis (immunohistochemistry/FACS), cell count/adhesion/distribution around the placenta (cell sorter, visual observation and counting), matrix metalloproteinase activity (zymogram) and estrogen receptor (ER) expression (western blotting, immunohistochemistry).


RESULTS
Reduced breast cancer cell numbers (45%↓, 48%↓ for MCF-7/T47D, respectively, P < 0.05) were observed near the placenta. The placenta elevated MCF-7 sub-G1 phase and modestly elevated apoptosis (3-17%↑ for T47D/MCF-7, respectively, P < 0.05). Our findings demonstrate breast cancer cell migration from the placenta as: (i) T47D/MCF-7 cells changed their morphology to that of motile cells; (ii) elevated MMPs activity was found in the co-culture; (iii) placental soluble factors detached breast cancer cells; and (4) the placenta reduced MCF-7/T47D cells' ER expression (a characteristic of motile cells).


CONCLUSIONS
MCF-7/T47D cells are eliminated from the placental surroundings. Analyzing the causes of these phenomena may suggest biological pathways for this event and raise new therapeutic targets.
Tartakover-Matalon
S
S
Oncogenetic Laboratory, Meir Medical Center, 45 Tschernehovski St, Kfar Saba 44281, Israel. matalon.shelly@clalit.org.il
Mizrahi
A
A
Epstein
G
G
Shneifi
A
A
Drucker
L
L
Pomeranz
M
M
Fishman
A
A
Radnay
J
J
Lishner
M
M
D017209:Apoptosis; D001943:Breast Neoplasms / Q000473:pathology*; D002448:Cell Adhesion; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D020782:Matrix Metalloproteinases / Q000032:analysis; D010920:Placenta / Q000473:pathology*; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000473:pathology*; D011261:Pregnancy Trimester, First; D011960:Receptors, Estrogen / Q000032:analysis
D011960:Receptors, Estrogen; D020782:Matrix Metalloproteinases