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| Status |
Public on Sep 07, 2017 |
| Title |
First trimester human placenta prevents breast cancer cell attachment to the matrix: the role of extracellular matrix |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The placenta is a nonsupportive microenvironment for cancer cells. We showed that breast cancer cells (BCCL) were eliminated from placental implantation sites. During implantation, the placenta manipulates its surrounding matrix, which may induce BCCL elimination. Here, we explored the effect of placenta-induced ECM manipulations on BCCL. During experiments, BCCL (MCF-7/T47D) were cultured on placenta/BCCL-conditioned ECM (Matrigel used for first trimester placenta/BCCL culture and cleared by NH4OH). After culturing the cells, we analyzed cancer cell phenotype (death, count, aggregation, MMP) and signaling (microarray analysis and pathway validation). We found that the BCCL did not attach to previous placental implantation sites and instead, similarly to anoikis-resistant cells, migrated away, displayed increased MMP levels/activity, and formed aggregates in distant areas. T47D were less affected than the MCF-7 cells, since MCF-7 also showed modest increases in cell death, EMT, and increased proliferation. Microarray analysis of the MCF-7 highlighted changes in the integrin, estrogen, EGFR, and TGFb pathways. Indeed, placental ECM reduced ERa, induced Smad3/JNK phosphorylation and increased integrin-a5 expression (RGD-dependent integrin) in the BCCL. Addition of RGD or TGFbR/JNK inhibitors reversed the phenotypic changes. This study helps explain the absence of metastases to the placenta and why advanced cancer is found in pregnancy, and provides possible therapeutic targets for anoikis-resistant cells.
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| Overall design |
Cells were cultured with or without placetal-conditioned extracellular matrix, and microarrays were used to estimate changes in gene expression.
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| Web link |
http://0-onlinelibrary-wiley-com.brum.beds.ac.uk/doi/10.1002/mc.22473/abstract
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| Contributor(s) |
Epstein Shochet G, Drucker L, Pomeranz M, Fishman A, Pasmanik-Chor M, Tartakover-Matalon S, Lishner M |
| Citation(s) |
26859229 |
| Submission date |
Sep 07, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Metsada Pasmanik-Chor |
| E-mail(s) |
metsada@tauex.tau.ac.il
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| Organization name |
Tel Aviv University
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| Department |
Biology
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| Lab |
Bioinformatics Unit
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| Street address |
Ramat Aviv
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| City |
Tel Aviv |
| ZIP/Postal code |
69978 |
| Country |
Israel |
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| Platforms (1) |
| GPL11532 |
[HuGene-1_1-st] Affymetrix Human Gene 1.1 ST Array [transcript (gene) version] |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA401987 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE103581_RAW.tar |
18.2 Mb |
(http)(custom) |
TAR (of CEL) |
| GSE103581_rma_gene_matrix.txt.gz |
651.8 Kb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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