H2020Individual fellowship2020–2022

MS · Unravelling the molecular and cellular mechanism of metastasis

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2020-01-29 → 2022-04-03
EU contribution
€178,320
Participants
3
Scheme
MSCA-IF-EF-ST

Lines connect the coordinator with its partners.

Results in brief

Unravelling the molecular and cellular mechanism of metastasis

The Marie Curie fellowship has enabled me to work on fundamental questions related to cancer and metastasis. Indeed, metastasis is the primary cause of cancer deaths. Yet, for most of cancers, the identification and the mechanisms by which the metastatic initiating cells (MICs) successfully establish a secondary tumor at a distant site from their primary tumor remains elusive. Understanding these mechanisms is fundamental in developing clinical applications that would enable the treatment of patients suffering from advanced-stage cancers. The understanding of such mechanisms would also enable a preventive approach for cancers detected early enough. The classical view of the metastatic process posits that MICs need to lose their cell-cell contact with the neighbors, detach from the primary tumor, intravasate into the blood circulation, circulate through the body, stop, extravasate and colonize distant organs, in which they reform a new mass of proliferative cells. With the tremendous heterogeneity of tumors and the limited capacity to trace multiple genetic clones in parallel with the traditional reporter mice , new animal models are needed to better understand the clonal dynamic and molecular mechanisms guiding different steps of the metastatic cascades in vivo. The overall objective of this project was to to investigate primary tumour heterogeneity and contribution of cancer clones to metastasis, as well as the role of microenvironment in regulating metastasis. This knowledge aids the design of new methods for early diagnosis and the monitoring of patients with metastasis, and will lead to new strategies that target or prevent metastasis.

Data: CORDIS, © European Union

Project 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.

Original text from CORDIS.

Participants

  • EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH · ZuerichCoordinatorSwitzerland
  • UNIVERSITAT BASEL · BaselSwitzerland
  • UNIVERSITE LIBRE DE BRUXELLES · Bruxelles / BrusselBelgium

Links

Data: CORDIS, © European Union