Breast cancer characteristics are modified by first trimester human placenta: in vitro co-culture study
| Autor: | Liat Drucker, Shelly Tartakover-Matalon, Michael Lishner, G. Epstein, A. Mizrahi, Ami Fishman, A. Shneifi, J. Radnay, Meir Pomeranz |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
medicine.medical_specialty
Placenta Estrogen receptor Apoptosis Breast Neoplasms Andrology Breast cancer Cell Movement Pregnancy Cell Line Tumor Internal medicine Cell Adhesion Humans Medicine skin and connective tissue diseases Cell Proliferation business.industry Cell Cycle Rehabilitation Obstetrics and Gynecology Cancer Trophoblast medicine.disease Coculture Techniques Matrix Metalloproteinases Pregnancy Trimester First Endocrinology medicine.anatomical_structure Receptors Estrogen Reproductive Medicine Cell culture Cancer cell Female Breast disease business Pregnancy Complications Neoplastic |
| Zdroj: | Human Reproduction. 25:2441-2454 |
| ISSN: | 1460-2350 0268-1161 |
| DOI: | 10.1093/humrep/deq227 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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