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2016 - Réalisé par ScientiWeb              Mentions légales

Digestive cancers

Axis 3

« Ongoing projects aim to study the molecular mechanisms responsible for ENS changes in colorectal cancer and also to study the existence of the same changes in gastric cancer»

Digestive cancers are among the most deadly of all cancers and despite therapeutic progress, their prognosis remains bleak. A better understanding of the mechanisms responsible for the development of these cancers would make it possible to identify new therapeutic targets and improve their prognosis. The environment close to the tumor (known as the "tumor microenvironment") is recognized as one of the main factors responsible for tumor development. The enteric nervous system (ENS) is one of the major components of this microenvironment and its role in carcinogenesis has been suggested by some studies. Our objective is to study the modifications of the ENS, and in particular of its two main constituents, the neurons and the glial cells, as well as the interactions between the ENS and the tumor cells, in the digestive cancers. We were interested in two types of cancer, colorectal cancer, the most frequent among digestive cancers, with more than 40,000 new cases per year in France, and gastric cancer characterized particularly by a poor prognosis with an overall survival not exceeding not 25%.

 

Our first results have shown that, in colorectal cancer, there are important changes in ENS (increase in neuronal density, change in neurochemical phenotype) that may play a role in the genesis and / or the spread of this cancer. We have also observed that the tumor cells preferentially adhere to the neurons and can migrate throughout them, this phenomenon being able to be responsible for the tumor dissemination (Figure 1). In addition, we have shown that some neurotransmitters such as acetylcholine, can stimulate the development of tumorospheres (Figure 2).

Figure 1 : Colorectal tumor cells (CT) adhere to enteric neurons. (A) Tumor cells (in green) adhere to enteric neurons (in red) without involving enteric glial cells (in white) in vitro (scale = 10μm). (B) Human tumor cells (in green) isolated from human colorectal cancers and cultured ex vivo preferentially adhere to enteric neurons (in red) (scale = 50μm).
Figure 2 : Acethylcholine stimulates tumorosphere development
Figure 3 : Tumor cells migrate along enteric neurons. Tumor cells of colorectal origin (in red) are able to migrate along enteric neurons (in green) (scale = 50μm).

Researchers / Clinicians

ITA/Students

Tamara Matysiak-Budnik

 

+33 2 40 08 31 51

tamara.matysiakbudnik@chu-nantes.fr

Yann Touchefeu

 

+33 2 40 08 31 51

yann.touchefeu@chu-nantes.fr

Michel Neunlist

 

+33 2 40 08 31 51

michel.neunlist@chu-nantes.fr

Thibauld Oullier

 

+33 2 40 41 29 50

thibauld.oullier@univ-nantes.fr

Anne Bessard

 

+33 2 40 41 29 50

anne.bessard@univ-nantes.fr

Emilie Duchalais

 

emilie.duchalais@gmail.com

Estelle Cauchin

 

+33 2 40 08 31 51

estelle.cauchin@chu-nantes.fr

Nicolas Chapelle.jpg

Nicolas Chapelle

 

+33 2 40 41

nicolas.chapelle@chu-nantes.fr

Publications

Nguyen PH, Touchefeu Y, Durand T, Aubert P, Duchalais E, Bruley des Varannes S, Varon C, Neunlist M, Matysiak-Budnik T. Acetylcholine induces stem cell properties of gastric cancer cells of diffuse type. Tumour Biol. 2018 Sep;40(9):1010428318799028. doi: 10.1177/1010428318799028

Duchalais E, Guilluy C, Nedellec S, Touvron M, Bessard A, Touchefeu Y, Bossard C, Boudin H, Louarn G, Neunlist M, Van Landeghem L. Colorectal Cancer Cells Adhere to and Migrate Along the Neurons of the Enteric Nervous System. Cell Mol Gastroenterol Hepatol. 2017 Oct 14;5(1):31-49.

Nguyen PH, Giraud J, Chambonnier L, Dubus P, Wittkop L, Belleannée G, Collet D, Soubeyran I, Evrard S, Rousseau B, Senant-Dugot N, Mégraud F, Mazurier F, Varon C. Characterization of Biomarkers of Tumorigenic and Chemoresistant Cancer Stem Cells in Human Gastric Carcinoma. Clin Cancer Res. 2017 Mar 15;23(6):1586-1597.

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