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PyMT-1099, a murine derived cell line is a breast cancer specific model for EMT

ABSTRACT: Background: Epithelial-mesenchymal transition (EMT) has been implicated in metastasis, drug resistance, survival under stress and also conferring stem cell-like traits to cancer cells. However, several of the studies have been carried out using model systems that don’t appropriately recapitulate all stages of the dynamic process of EMT. Hence, there is a need to overcome this limitation by development of a model system that allows us to mimic each stage of EMT and accurately assess the plastic changes associated with it. Methods: We have derived a cancer cell line from the PyMT-MMTV model of breast cancer, named PyMT-1099 cells, and undertaken a detailed characterization of the morpho-genetic changes it undergoes during a TGF-induced EMT. Further, we have also performed high throughput transcriptomics on PyMT-1099 cells undergoing EMT in a high resolution kinetic of TGF treatment. Results: We show that PyMT-1099 cells undergo an EMT comparable to the classically used immortalized NMuMG cells as assessed by morphological, and marker expression changes on TGFtreatment. Further, PyMT-1099 cells can also migrate in vitro in response to TGF treatment. These cells are also tumorigenic and lead to metastasis formation when transplanted into immunocompromised mice. Conclusion: In this study we report the development of PyMT-1099 cells as an excellent tool to model and study breast cancer-associated EMT both in vitro and in vivo and show that these cells overcome the limitations posed by other cellular systems currently being used to study EMT

ORGANISM(S): Mus musculus

PROVIDER: GSE114572 | GEO | 2018/10/03

REPOSITORIES: GEO

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Mesenchymal Epithelial Transition (MET) Timecourse of NMuMG-E9 cells treated with TGFb

Project description:Background: Epithelial-mesenchymal transition (EMT) has been implicated in metastasis, drug resistance, survival under stress and also conferring stem cell-like traits to cancer cells. However, several of the studies have been carried out using model systems that don’t appropriately recapitulate all stages of the dynamic process of EMT. Hence, there is a need to overcome this limitation by development of a model system that allows us to mimic each stage of EMT and accurately assess the plastic changes associated with it. Methods: We have derived a cancer cell line from the PyMT-MMTV model of breast cancer, named PyMT-1099 cells, and undertaken a detailed characterization of the morpho-genetic changes it undergoes during a TGFbeta-induced EMT. Further, we have also performed high throughput transcriptomics on PyMT-1099 cells undergoing EMT in a high resolution kinetic of TGFbeta treatment. Results: We show that PyMT-1099 cells undergo an EMT comparable to the classically used immortalized NMuMG cells as assessed by morphological, and marker expression changes on TGFbeta treatment. Further, PyMT-1099 cells can also migrate in vitro in response to TGFbeta treatment. These cells are also tumorigenic and lead to metastasis formation when transplanted into immunocompromised mice. Conclusion: In this study we report the development of PyMT-1099 cells as an excellent tool to model and study breast cancer-associated EMT both in vitro and in vivo and show that these cells overcome the limitations posed by other cellular systems currently being used to study EMT

2018-10-03 | GSE117474 | GEO

PyMT-1099, a murine derived cell line is a breast cancer specific model for EMT

Project description:PyMT-1099, a murine derived cell line is a breast cancer specific model for EMT

| PRJNA471818 | ENA

Single cell sequencing of Tri-PyMT cells

Project description:To study the contribution of epithelial-to-mesenchymal transition (EMT) in tumor metastasis, we established an EMT lineage tracing model in a multiple-transgenic mouse (MMTV-PyMT/Fsp1-Cre/Rosa26mT/mG, Tri-PyMT). In this model, breast tumor cells that underwent EMT would irreversibly switch their expression of the fluorescent marker from RFP+ to GFP+ due to the mesenchymal specific Cre expression. Surprisingly, we found that metastatic tumor cells did not convert from RFP+ to GFP+. Lung metastases were predominantly composed of RFP+ tumor cells persistently exhibiting epithelial phenotypes. These findings challenge the concept that EMT is required for metastasis, and have attracted vigorous discussion about its true contributions to metastasis. One of the major concerns with the EMT lineage tracing model is that expression of GFP only indicates the complete EMT transition. The partial-EMT programming, a novel concept describing tumor cells exhibiting both epithelial and mesenchymal features, could possibly fail to launch the Fsp1-Cre-mediated fluorescent marker switch. To address this concern, we evaluated the EMT status of Tri-PyMT cells on the single cell level by performing single cell RNA-sequencing (scRNA-seq). We found that the expression of epithelial markers (i.e. Epcam and Krt18) and mesenchymal markers (i.e. Vim and S110a4) were largely confined to RFP+ and GFP+ subpopulations, respectively. Based on the differentially expressed EMT related genes, we observed an EMT spectrum in which the low EMT score end was enriched with RFP+ cells, whereas the high EMT score end was enriched with GFP+ cells. Indeed, the fluorescent marker switch in Tri-PyMT cells predicted their EMT status with high specificity and sensitivity. Tri-PyMT cells which were derived from the primary breast tumor of triple transgenic mouse (MMTV-PyMT:Fsp1-cre:Rosa26mT/mG) were sorted into RFP+ or GFP+ populations by FACS and subjected for Drop-seq analysis.

2022-02-01 | GSE126374 | GEO

CdGAP is a Talin-binding protein and a target of TGF-β signaling that promotes HER2-positive breast cancer growth and metastasis

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2023-07-14 | PXD043376 | Pride

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Project description:Epithelial-mesenchymal transition (EMT) is a multistep process of cell de-differentiation which confers carcinoma cells with a variety of malignant characteristics. Due to the transient and reversible nature of the process, cancer cells may transit between various stages of an EMT continuum, including epithelial, partial EMT or full EMT, and the actual status of cancer cells, the kinetics of cellular state transition in vivo and the consequences thereof have remained elusive. We have established tamoxifen inducible dual recombinase lineage tracing systems combined with live cell imaging and 5-cell RNA-sequencing analysis to track cancer cells undergoing a partial or a full EMT in the MMTV-PyMT mouse model of metastatic breast cancer. In primary tumours, cancer cells infrequently undergo an EMT, and most of these cells transition between epithelial and partial EMT states, but rarely undergo a full EMT. Consequently, cells that have ever undergone a partial EMT dynamically transit between various EMT states, and they contribute to lung metastasis and chemoresistance. In contrast, full EMT cells mostly retain a mesenchymal phenotype and stably reside in perivascular regions, but fail to colonize the lungs. However, full EMT cancer cells are enriched in recurrent tumors upon chemotherapy. Our findings suggest that cancer cells in various stages of the EMT continuum contribute differentially to hallmarks of breast cancer malignancy, such as cell migration, invasion, metastasis and chemoresistance.

2021-11-18 | GSE171940 | GEO

Expression data from Control and Six1 expressing MCF7 cells

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Drosha/Dicer/miR-7/TGF-β2 axis Sustained Acidic Microenvironment-induced Lung Metastasis

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2022-04-01 | PXD016524 | Pride

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2023-03-25 | GSE193155 | GEO

RNA N6-methyladenosine reader YTHDC1 is essential for TGF-beta-mediated metastasis of triple negative breast cancer [RIP-Seq]

2023-03-25 | GSE193154 | GEO

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