Understanding the mechanisms & mechanics
of tumor metastasis & dissemination
RESEARCH
The TUMOR BIOMECHANICS LAB has several RESEARCH INTERESTS
We study how tumor cells grow and disseminate,
We study how they prime metastatic niches at distance,
We study how they exploit mechanical forces to form metastasis,
We study how they acquire therapy resistance and finally how we can circumvent that.
We use state-of-the-art cellular and molecular biology approaches,
We rely on a variety of photonic and eletronic imaging approaches
Which we apply on two highly complementary animal models, mouse and zebrafish.
The TUMOR BIOMECHANICS LAB structure
EXPLORE : lead by V.Hyenne
We study the priming of metastatic niches by extracellular vesicles
FORCE : lead by N.OSMANI
We dissect mechanical forces in metastasis & immunosurveilance
RESIST : lead by C.DOMON-DELL
We study mechanics of oncogenesis & resistance of B-ALL
EARLY : lead by I.DULUC
We investigate the early dissemination of colon cancer
TREAT : lead by O.LEFEBVRE
We develop anti-tumoral and anti-metastatic strategies
EXPLORE
We try to understand how tumor cells manipulate their microenvironment to favor metastasis. We focus on the role of tumor secreted extracellular vesicles in the communication with stromal cells: how are they made ? What do they contain ? Where do they go ? What do they do ? In addition, we dissect the contribution of other organelles, such as lysosomes, along the metastatic cascade.
Key publications:
FORCE
We study how cellular mechanical properties and environmental biomechanical features tune metastatic dissemination, cancer cell phenotypes and their interaction with other cell types.
We focus on the vascular dynamics of circulating tumor cells and study their interaction with endothelial cells during arrest and extravasation, as well as with other blood components.
Key publications:
Mittelheisser et al. Evidence & therapeutic implications of biomechanically regulated immunosurveillance in cancer Nature Nanotechnology 2024
Gensbittel et al. Mechanical Adaptability of Tumor Cells in Metastasis. Developmental Cell 2021
Follain et al. Fluids and their mechanics in tumour transit: shaping metastasis Nature Reviews Cancer 2020
Osmani et al. Metastatic Tumor Cells Exploit Their Adhesion Repertoire to Counteract Shear Forces during Intravascular Arrest Cell Reports 2019
Follain et al. Hemodynamic Forces Tune the Arrest, Adhesion, and Extravasation of Circulating Tumor Cells Developmental Cell 2018
RESIST
We aim at understanding the biology of adult B-ALL and how the drug resistance arises. We are developing mouse models to recapitulate leukemogenesis and PDX to investigate in vivo the distribution of leukemia cells into the bone marrow. How do treatment-resistant leukemia cells acquire a dormant/leukemic stem cell phenotype
to escape treatment? How can the microenvironment influence and
protect these cells? Is there a specific spatial distribution of resistant cells into the bone marrow?
Key publications:
Passet et al. Concurrent CDX2 cis-deregulation and UBTF::ATXN7L3 fusion define a novel high-risk subtype of B-cell ALL. Blood 2022
Galland et al. CDX2 expression in the hematopoietic lineage promotes leukemogenesis via TGFβ inhibition. Mol. Oncology 2021
El Omar et al. CDX2 regulates ACE expression in blood development and leukemia cells. Blood Adv. 2021
EARLY
We study the consequences of intra-tumoral heterogeneity on the early tumor dissemination properties, using intestinal tumors as a model. We develop innovative cell models harboring distinct and permanent fluorescence traceability representative of the intratumoral heterogeneity. How quickly do tumors disseminate ? Can we track this in vivo ?
Key publications:
Balbinot et al. The Cdx2 homeobox gene suppresses intestinal tumorigenesis through non–cell-autonomous mechanisms J Exp Med 2018
Benahmed et al. Multiple Reg. Regions Control the Complex Expression Pattern of the Mouse Cdx2 Homeobox Gene Gastroenterology 2008
Benahmed et al. The Microenvironment Controls CDX2 Homeobox Gene Expression in Colorectal Cancer Cells Am J Path 2007
TREAT
We develop and manipulate pre-clinical models that allow us to functionnaly test the relevance of our findings as well as to test anti-tumoral or anti-metastatic strategies. The ultimate goals are to provide pre-clinical relevance for our discoveries as well as to identify new and promising therapeutic schemes relevant for cancer treatment.
Key publications:
Garcia-Leaon et al. Platelets favor the outgrowth of established metastases Nat Commun 2024
Mittelheisser et al. Optimal physicochemical properties of antibody–nanoparticle conjugates for improved tumor targeting Adv Mat 2022
Liu et al. Drug‐Sponge Lipid Nanocarrier for in Situ Cargo Loading and Release Using Dynamic Covalent Chemistry Angew Chemie 2021
Bouchaala et al. Integrity of lipid nanocarriers in bloodstream & tumor quantified by near-IR FRET imaging in living mice J Control Release 2016
