Cancer Models
Engineered Microenvironments to Probe Cancer Cell Behavior
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Quantification of migration behaviors and migration transitions
Quantification of contractility of cancer cells
Cell migration in cancer assay
Analysis of cell behaviors during metastasis
Cancer nuclear mechanics
CANCER INVASIVENESS ASSAY
Quantification of migration behaviors and migration transitions
4Dcell technology
SmartConfiner Technology
Read-outs
Cell adhesion, quantification of cell migration speed, cell migration phenotype, cell migration transition
Standard culture limitation
Most cells on a flat surface show a “mesenchymal”-like migration behavior which is not representative of their in vivo behavior.
Cancer invasiveness assay benefits
In an environment controlled at the adhesiveness and confinement level, migration transitions (e.g. mesenchymal to amoeboid – MAT) can be triggered, observed and characterized (quantified).
Example
Slow mesenchymal cells can switch to fast amoeboid-like migration under conditions of low adhesion and strong confinement [1].
References
[1] Liu, Y.-J., et al. Cell. 2015 Feb 12;160(4):659-672
CANCER AGRESSIVENESS ASSAY
Quantification of contractility of cancer cells
4Dcell technology
SmartConfiner Technology
Read-outs
Cell contractility, cell stiffness
Standard culture limitation
Contractility is an important hallmark of cancer aggressivity, but no commercial assay actually allows its quantification.
Contractility assay benefits
After confinement of cells between two layers of non-adhesive gels of controlled stiffness, cells round up proportionally to their contractile activity. A relevant index is extracted relying only on the contractile activity of the cell.
Example
Contractility measurement of HeLa cells in between gels with a stiffness of 1 kPa [1].
References
[1] Liu, Y.-J., et al. Cell. 2015 Feb 12;160(4):659-67
CELL MIGRATION IN CANCER ASSAY
Analysis of cell behaviors during metastasis
4Dcell technology
SmartChannel Dishes
Read-outs
Observation of cell motility and quantification of migration speed
Standard culture limitation
Cancer is considered a localized disease in its early stages. However, in the process of metastasis, cancer cells of a typical solid tumor must loosen their adhesion to neighboring cells and escape from the tissue of origin. Subsequently, cancer cells invade other tissues by degrading the extracellular matrix until they reach a blood or lymphatic vessel to enter circulation. Lastly, the cells reach the new environment whereby they will proliferate and ultimately reside. Those physiological constraints are difficult to reproduce in a standard cell culture system.
Cell migration in cancer assay benefits
Using 4Dcell microchannels, natural constraints can be reproduced to mimic the trajectory of cancer cells spreading away from the primary tumor.
Example
Motility of breast cancer cells in 3 µm channels (filled circles) and in 12 µm channels (empty squares) [2]
Motility can be measured and is better maintained in 12 µm channels.
Schematic representation of the motion of aggregated HeLa cells passing through a microcapillary to seed distant tumor [2]
Live and metastatic cells can be observed after passing through a constriction.
NUCLEAR DEFORMATION ASSAY
Cancer nuclear mechanics
4Dcell technology
SmartConfiner Technology
SmartChannel Technology
Read-outs
Nuclear membrane rupture, nuclear membrane re-sealing, nuclear deformation, gene expression, etc.
Cell type
Fibroblast, cancer cells, immune cells, endothelial cells, stem cells, neurons
Field of research - Applications
Biophysics, mechanotransduction and tissue engineering, cancer and metastasis, cell senescence and aging, neurobiology, immune response, and others
Example
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Dynamic confiners – Mechanobiology
Dantas et al. Nuclear tension controls mitotic entry by regulating cyclin B1 nuclear translocation. JCB, 2022
In this manuscript the authors used our dynamic confiners with two confinement hights, 8µm that corresponds to a low confinement pressure for their epithelial cell model (RPE cells) and 3µm that results in high confinement condition for RPE. By using nuclear localisation signal (NLS in green) as a proxy for nuclear envelope rupture, the authors observed leakage of NLS in the cytoplasm in the condition of high confinement (3µm)
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Microchannels – Cancer and metastasis
Chen YQ et al. Snail Augments Nuclear Deformability to Promote Lymph Node Metastasis of Head and Neck Squamous Cell Carcinoma. Front Cell Dev Biol, 2022
In this manuscript the authors used our microchannels of different heights (12, 16 and 18µm) to confine and induce nuclear deformation of cells head and neck squamous carcinoma (HNSCC) cells derived from mice with lymph node metastasis (SAS-LN) and without lymph node metastasis (SAS). At the high confinement condition of 12µm, the authors observed that the SAS-LN were able to migrate better in the microchannels (more cells) and that the nuclei were elongated (30 µm in SAS-LN versus 20 µm of SAS). This suggested that the nuclear flexibility could confer HNSCC an advantage in tissue invasion and metastasis.