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  • Mid-Term Report Summary - SIGNALING 3D (Three Dimensional Single Cell Analysis of the Cancer Stem Cell Inducing Epithelial-Mesenchymal Transition Signaling Networks in Breast Cancer by Mass Cytometry)
ERC

Signaling 3D Report Summary

Project ID: 336921
Funded under: FP7-IDEAS-ERC
Country: Switzerland

Mid-Term Report Summary - SIGNALING 3D (Three Dimensional Single Cell Analysis of the Cancer Stem Cell Inducing Epithelial-Mesenchymal Transition Signaling Networks in Breast Cancer by Mass Cytometry)

Tumor metastasis are the main cause of cancer patient mortality. In breast cancer, a process called epithelial-mesenchymal transition (EMT) is a key process for the generation of treatment resistant cancer stem cells and to drive the metastatic dissemination of tumor cells. The EMT is controlled by regulatory circuits that upon activation orchestrate the process. Responsible for the activation are frequently signals of the environment of a cell.
We comprehensively studied the structure of the regulatory circuits using a recent single cell analysis technology, called mass cytometry. In mass cytometry, metal isotopes are used as reporters to mark cellular components of interest. By mass cytometry, up to 100 cellular components can be measured simultaneously. Using computational modeling, we understood the regulatory circuit of EMT to the extent that we can now predict how to block and even accelerate the process. These predictions were experimentally verified. To understand cell-to-cell communication and the cellular activation of EMT in breast cancer tissues, we developed a new imaging technology which we termed "imaging mass cytometry". Here a laser ablation system is coupled to a mass cytometer and up to 100 markers can be imaged at subcellular resolution on cancer tissues. Together with novel data analysis tools that we have developed for this novel type of multiplexed images, we currently use the approach to shed light on which cells in breast tumors become metastatic via an EMT and which signals of a cells environment trigger this process.
In summary, we have developed a novel tissue imaging technology and used single cell systems biology analysis to understand the regulatory circuits that govern breast cancer cell dissemination and the generation of cancer stem cells.

Reported by

UNIVERSITAET ZUERICH
Switzerland
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