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In vitro platform mimics the tumor microenvironment of pancreatic cancer

​Using almost fully automated processes, researchers at our laboratory have designed a 3D microenvironment in which cells can form a microtumor-like tissue. They showed that the biomimetic film they developed can mimic the biophysical conditions of the tumor microenvironment, including stiffness and the delivery of adhesion proteins and growth factors. Their work will open up perspectives for drug testing on mini-tumors in the context of personalized medicine.

Published on 21 June 2022
Studying cancer cell mechanisms is impaired by the lack of diagnostic tools and the limitations of current models. Conventional cultures performed on a plastic or glass support for cell culture are unable to reproduce the biophysical and biochemical conditions of the tumor microenvironment, since they are far too rigid. In vivo, the tumor has a three-dimensional (3D) organization and is surrounded by an extracellular matrix of proteins and growth factors. In vivo animal models have been developed, but the procedures to form these tumoral models are long, costly and raise several ethical concerns. Therefore, there is a need to develop new in vitro models that mimic the in vivo tumor microenvironment at all stages of development, so that the cells can ultimately form a 3D mini-tumor. Such models allow to precisely control the effect of different experimental parameters.

Cancer cells require an appropriate environment composed mainly of extracellular matrix proteins for biochemical and structural support, and growth factors to influence cellular responses. The extracellular matrix is an entangled network of proteins, sugars and growth factors, which allows cancer cells to communicate with each other through biochemical and mechanical signals. Its composition and rigidity have a significant impact on tumor mechanisms. To mimic the composition of this matrix, it is possible to use polyelectrolyte multilayer films prepared by the layer-by-layer assembly technique: the architecture, thickness, chemistry and mechanical properties of the films can be controlled so that biomimetic films can be engineer to deliver drugs and proteins acting on human cells.

In this work, using almost fully automated processes, the researchers created a synthetic, bioactive 3D microenvironment for cancer cell growth, self-organization, migration and proliferation to form a three-dimensional microtumor-like tissue. In this new 3D environment, pancreatic cell adhesion and proliferation was found to be influenced by mechanical and biochemical signals provided by the biomimetic film in a cell type-specific manner. In particular, bone morphogenetic proteins 2 and 4 appear to be important factors in pancreatic cancer.
On longer term, this work opens perspectives for drug testing on mini-tumors in the context of personalized medicine. 

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