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Research project
Understanding the metastasis cascade: still a long way ahead
Metastasis can be considered as the end product of a multistep bio-mechano-chemical process where cancer cells disseminate to distant organs and home in a new tissue microenvironment (Fig.1). Metastases are resistant to multiple therapies and are responsible for the large majority of cancer-related deaths. It is now clear that the invasion-angiogenesis-metastasis cascade is not only dependent on genetic and epigenetic alterations within cancer cells, but also involves non-neoplastic stromal cells that contribute to cancer progression. However, the molecular and cellular mechanisms driving metastasis formation remain to be elucidated and better described in a realistic in vivo context. In this context, tumor cells interact with their surrounding microenvironment and corrupt it to their own benefit. For example, exosomes are small extracellular vesicles, which recently emerged as potent mediators involved in this communication. These vesicles are from an endosomal origin, contain proteins, mRNAs, non-coding RNAs and DNA; they circulate in all our body fluids and can be internalized by specific distant cells and ultimately deliver a functional message. Tumor cells release large amounts of exosomes bearing tumoral markers, which can subsequently disseminate at distance. In addition, tumor exosomes contain pro-metastatic factors that shape pre-metastatic niches (PMN), before the actual arrival of tumor cells, while determining tumor metastatic organo-tropism. These properties have promoted exosomes as new targets for anti-tumoral therapies and major candidates for non-invasive diagnosis in cancer using liquid biopsies (blood and urine), and intense research is currently conducted to identify exosome-carried biomarkers.
MAJOR COLLABORATIONS
Jochen GUCK (MPI, Erlangen) : Cell Mechanics, Hector PEINADO (CNIO, Madrid), Julie GAVARD (Nantes) : EVs, Yannick SCHWAB (EMBL, Heidelberg) : Correlative microscopy, Sylvain GIOUX (ICube, Strasbourg), Frank WINKLER (DKFZ, Heidelberg): Intravital imaging, Pierre MANGIN (EFS, Strasbourg): Hemodynamics, Andrey KLYMCHENKO and Nicolas ANTON (Faculté de Pharmacie, Strasbourg): Intravital imaging and tumor targeting, Philippe CHAVRIER and Matthieu PIEL (Curie, Paris): Correlative microscopy of the metastasis cascade.
FUNDING
- Ongoing: ARC (Cancer Research Association) (2018-2021) in a collaborative project, INCA (National French Cancer Agency) grant (2015-2019), Plan Cancer (French Cancer Research Plan) grant (2015-2019), INCA (National French Cancer Agency) in a collaborative project (2015-2019), INCA (National French Cancer Agency) in a collaborative project (2016-2019), Ligue contre le Cancer (2019), Canceropole Est Interregional grant (2018-19)
- Finalized: SATT Conectus (2018) grant, Canceropole Est cross-border grant (2016), Roche fundamental Research grant (2014), Ligue contre le Cancer (2013-14-17-18), University of Strasbourg starting grant (2012-13), Marie Curie IEF Post-doctoral fellow (2010-2010), CNIC Post-doc fellowship (2008-10), ARC (Cancer Research Association) Ph.D fellowship (2007), French Ministry Ph.D fellowship (2003-06)
