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Unravelling the molecular and cellular mechanism of metastasis

Project description

Understanding why the 'metastasisers' colonise and other circulating cancer cells do not

The primary reason cancer is so serious is its ability to spread to distant parts of the body. Metastasis is the leading cause of cancer-related deaths yet the mechanisms have remained elusive. Tumours constantly shed cells that travel systemically throughout the body but only a small fraction of these colonise other tissues and initiate tumour formation. Increasing research has focused on populations of cells called metastasis-inducing cells (MICs). The EU-funded MS project is driving the innovation required to address this pressing therapeutic domain. Using two novel mouse models of cancer and high-tech genetics techniques, the team hopes to elucidate details of the cellular and molecular mechanisms underlying metastases.

Objective

Metastasis is the primary cause of cancer deaths. For most cancers, the identification and the mechanisms by which the metastatic initiating cells (MICs) successfully establish a secondary tumour at a distant site from their primary tumour remains elusive (1). New animal models are needed to better understand the clonal dynamic and molecular mechanisms guiding different steps of the metastatic cascades in vivo, given the tremendous heterogeneity of tumours (2-7) and the limited capacity to trace multiple genetic clones in parallel with the traditional reporter mice (8). This will aid the design of new methods for early diagnosis and the monitoring of patients with metastasis, as well as the development of new strategies that target or prevent metastasis.

In this project, I will use clonal lineage tracing with Poly-Lox reporter that enables tracing of over 200’000 clones (9) and confetti reporter (10) combined with single cell transcriptional profiling in order to define the cellular and molecular mechanisms that regulate the metastatic cascade in vivo in two different mouse models of squamous cell carcinoma and breast tumour. With the immunostaining, FACS and single cell sequencing analyses I will study the role of various fibroblast sub-populations in affecting the extravasion and establishment of tumour cells at the site of metastasis.

Fields of science (EuroSciVoc)

Programme(s)

Topic(s)

Funding Scheme

MSCA-IF-EF-ST - Standard EF

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Call for proposal

(opens in new window) H2020-MSCA-IF-2018

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Coordinator

EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Net EU contribution
€ 77 670,93
Address
Raemistrasse 101
8092 Zuerich
Switzerland
Region
Schweiz/Suisse/Svizzera Zürich Zürich
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 77 671,65

Participants (2)