MS | Unravelling the molecular and cellular mechanism of metastasis

Summary
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.
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/847012
Start date: 29-01-2020
End date: 03-04-2022
Total budget - Public funding: 178 320,72 Euro - 178 320,00 Euro
Cordis data

Original description

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.

Status

CLOSED

Call topic

MSCA-IF-2018

Update Date

28-04-2024
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Horizon 2020
H2020-EU.1. EXCELLENT SCIENCE
H2020-EU.1.3. EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions (MSCA)
H2020-EU.1.3.2. Nurturing excellence by means of cross-border and cross-sector mobility
H2020-MSCA-IF-2018
MSCA-IF-2018