Date post: | 11-Apr-2017 |
Category: |
Science |
Upload: | rsg-luxembourg |
View: | 48 times |
Download: | 0 times |
S
Epithelial-mesenchymal transition
Kamil Grzyb PhD student at ICS
LCSB
What is EMT (or MET)
Where EMT is present
S EMTs are associated with S embryo implantation,
S embryogenesis,
S organ development,
S wound healing
S But also contributes pathologically to fibrosis or cancer metastasis
Cancer metastasis with EMT
Nature 493, 487–488 (24 January 2013)
Triple-transgenic mouse model
ü Mouse models of breast cancer metastasis (MMTV - PyMT) ü Fsp1 is the critical gatekeeping gene of EMT initiation ü Cre-switchable fluorescent marker under the control of the �-actin
promoter (Rosa26) – irreversible!
Confirming the E(RFP+) and M(GFP+) phenotype
Primary tumor & lung metastasis stained
Tumor graft for EMT
2% GFP+ 98% RFP+
GFP+ EMT tumour cells did not contribute to lung metastasis
Validating EMT lineage tracing system
EMT lineage tracing system
Almost no Mesenchymal
originated metastasis
In vivo spreading of tri-PyMT cells.
Inhibit EMT with miR-200
M cells chemoresistance(CTX)
• Mice treated with cyclophosphamide (CTX) • 60% tumor reduction (by êgrowth and éapoptosis) • GFP+(mesenchymal) cell count remained static.
miR-200 cancel M resistance
RNA-sequencing
Summing up…
S Tumour cells disseminate and form metastases while persisting in their epithelial phenotype.
S miR-200 (EMT inhibitor) has no effect on metastasis
S Non-EMT cells are sensitive to chemotherapy
Other ways that EMT possibly contribute to cancer metastasis?
Tamoxifen-Cre