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Mechanobiology of Disease
Poster Abstracts
48
13-POS
Board 13
Study of the Metastatic Process of Circulating Tumour Cells by Organ-on-a-Chip in Vitro
Models
Hamizah Cognart
1,2,3
, Catherine Villard
1,2,3
, Jean-Louis Viovy
1,2,3
.
1
Institut Curie, Paris, France,
2
Sorbonne Universités, Paris, France,
3
Institut Pierre-Gilles de
Gennes, Paris, France.
90% of cancer mortality arises from metastases, due to cells that escape from a primary tumour,
circulate in the blood as circulating tumour cells (CTCs), leave blood vessels and nest in distant
organs. The processes by which CTCs invade distant organs, remodel their environment to create
a “micrometastatic niche”, the eventual triggering of a proliferation leading to a macroscopic
metastases, are poorly known, mostly because of a lack of experimental models. These events
are rare; occur in the body at unknown places and on a microscopic scale.
The loss of cell adhesion of tumour cells detaching from the primary tumour tissues will undergo
a transformation phenomenon known as epithelial-to-mesenchymal transition (EMT) leading to
the lost of epithelial characteristics with different expression patterns of EMT markers (E-
cadherin, N-cadherin, Vimentin, Snail, Twist). EMT is believed to play a key role in metastasis,
as it is a morphogenetic transformation in which epithelial tumour cells lose their epithelial
characteristics and acquire a mesenchymal-like phenotype to increase cell motility and plasticity
allowing dissemination of these tumour cells in blood circulation to distant sites.
Here, we designed and fabricated microfluidic models containing mechanical constrictions in
order to mimic the blood microcirculation. Metastatic breast cancer cells, MDA-MB-231, and
epithelial Madin-Darby canine kidney (MDCK) cells are subjected and confined to the
microfluidic channels using a flow control system. These cells are circulated under optimal
culture conditions, and monitored in the channels for the observance of biophysical occurrences
from continuous mechanical cellular deformations. We would like to study the biophysical
effects of circulation and confinement on tumour cell morphogenesis.