In vitro platform mimics pancreatic cancer tumor microenvironment

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Using almost fully automated processes, Irig researchers have designed a 3D microenvironment in which cells can form mini-tumor-like tissue. The biomimetic film they developed can mimic the biophysical conditions of the tumor microenvironment, including stiffness and protein delivery ofmembership (In physics, adhesion is the set of physico-chemical phenomena that occur…) and growth factors. Their work will open up prospects for drug tests on mini-tumors in the context of medicine (Medicine (from the Latin medicus, « that heals ») is the science and the…) personalized.

The study of the mechanisms of cancerous cells comes up against the lack of tools for diagnostic (The diagnosis (from the Greek δι?γνωση, diágnosi, from…) and the limitations of existing models. Conventional cultures grown on a plastic support for Culture (The Culture is a pan-galactic civilization invented by Iain M. Banks through his…) tissue are unable to reproduce the biophysical and chemical conditions of the tumor microenvironment. Moreover, the experimental models are not physiological because the cells are cultured on materials (A material is a material of natural or artificial origin that man shapes to…) rigid (plastic or glass). [i]In-vivo (In vivo (in Latin: « within the living ») is a Latin expression…)the tumor (The term tumor (from the Latin tumere, to swell) designates, in medicine, an increase in…) is organized into a architecture (Architecture can be defined as the art of constructing buildings.) three-dimensional and is surrounded by an extracellular matrix. Models live have been developed, but the procedures to obtain them are long, expensive and raise many ethical issues related to animal handling. It is therefore necessary to develop new models in vitro that mimic the tumor microenvironment live at all stages of development so that cells can eventually form a three-dimensional (3D) tumor. Such models make it possible to precisely control the effect of the experimental conditions.

Cancer cells have need (Needs are at the level of the interaction between the individual and the environment. It is…) of one environment (The environment is everything that surrounds us. It is all the natural elements and…) suitable compound primarily of extracellular matrix proteins for biochemical and structural support, growth factors to mediate cellular responses. The extracellular matrix is ​​a network (A computer network is a set of equipment linked together to exchange information…) entangled with 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 imitate the composition of this matrix, it is possible to use multilayer films of polyelectrolytes prepared by the layer-by-layer assembly technique which make it possible to adjust the architecture, the thickness, the chemistry (Chemistry is a natural science divided into several specialties, to…) and the mechanical properties of films and to develop biomimetic nanofilms to deliver drugs and proteins acting on human cells.

Based on their previous experimental work, researchers at Irig have selected films based onhyaluronic acid (Hyaluronic acid (from the Greek hyalos = vitreous + uronic because it was first…)one of the main constituents of skin (The skin is an organ composed of several layers of tissue. It plays, among other things, the…)and poly(L-lysine), a polypeptide widely used in culture (The UNESCO definition of culture is as follows [1] 🙂 cellular. After elaboration, these films were then chemically cross-linked to modulate their rigidity then, in a last step, proteins were loaded into the films. Thus, the films exhibit two main characteristics of the extracellular matrix: a controlled rigidity and a reserve of protein (A protein is a biological macromolecule composed of one or more…)to then present them to the cells over a long period of weather (Time is a concept developed by human beings to apprehend the…).

As part of this work, using almost entirely automated processes, the Irig researchers created a synthetic and bioactive 3D microenvironment in which they observed that cancer cells self-organize, migrate and proliferate to form a microtumor-like tissue in three dimensions (In common sense, the notion of dimension refers to size; the dimensions of a room…). This new 3D environment allowed them to show that the adhesion and proliferation of cancer cells of the pancreas (The pancreas is an abdominal organ, a gland attached to the digestive tract. It is…) were influenced by biomechanical and biochemical signals from the biomimetic film, in a cell type-specific manner. In particular, type 2 and 4 bone morphogenetic proteins appear to be important factors in the cancer (Cancer is a disease characterized by abnormal cell proliferation…) of the pancreas.

In the longer term, this work opens up prospects for drug tests on mini-tumors in the context of personalized medicine.

Division of a metastatic cell. Credit: Getty

References:

Rengaraj A, Bosc L, Machillot P, McGuckin C, Milet C, Forraz N, Paliard P, Barbier D and Picart C
Engineering of a microscale niche for pancreatic tumor cells using bioactive film coatings combined with 3D-architectured scaffolds.
ACS Applied Materials & Interfaces2022.