Le mercredi 13 novembre 2024, Madame Isabelle BOURGOT, titulaire d’un Diplôme de docteur en médecine vétérinaire d’un Certificat de formation à la recherche en sciences biomédicales et pharmaceutiques, présentera l'examen en vue de l'obtention du grade de Doctorat en sciences biomédicales et pharmaceutiques, sous la direction de Madame Agnès NOËL et de Monsieur Erik MAQUOI.

Cette épreuve consistera en la défense publique d'une thèse intitulée :  "Insight into the contribution of cathepsin B during cancer-associated fibroblast migration in a three dimensional collagen matrix".

Le jury sera composé de :

Ingrid STRUMAN (Présidente), Alain COLIGE (Secrétaire), Niels BEHRENDT (Univ. Copenhague), Olivier DE WEVER (UGent), Philippe DELVENNE, Chantal HUMBLET, Erik MAQUOI, Agnès NOËL.

Résumé de la thèse :

Tumors arise in a complex ecosystem governed by interactions established between heterogenous cell types and extracellular matrix components, which compose the tumor microenvironment. Cancer-associated fibroblasts (CAFs) represent not only a major component of solid tumors but are essential for tumor progression since they play a central role in the desmoplastic reaction by promoting matrix deposition and remodelling. Nevertheless, the entire functions of CAFs in cancer progression are not fully understood. In this work we focus on cathepsin B (Ctsb), a cysteine protease expressed by cancer cells and tumor-associated macrophages, promoting tumor growth and metastasis notably in breast cancer. By using the MMTV-PyMT mouse model of breast cancer, we observe that CAFs express Ctsb at higher levels than cancer cells. However, the contribution of CAF-derived Ctsb to tumor progression is unknown. In this work, we have focused on the invasion of CAFs through a three-dimensional (3D) collagenous microenvironment. For that purpose, an in vitro spheroid invasion assay in 3D fibrillar collagen combined with a 3D/4D computer-assisted quantification method was developed. Our data revealed that Ctsb deficiency diminishes the capacity of CAFs to interact with collagen fibres and compromises their migration. We further deciphered the mechanisms accounting for the Ctsb pro-invasive function.