Microenvironnement and Therapeutic Resistance
in Pancreatic Neoplasms


Pancreatic ductal adenocarcinoma (PDAC), commonly known as pancreatic cancer, is a very aggressive tumor since it presents a rapid metastatic potential and a strong therapeutic resistance. This tumor has the particularity of being rich in stroma (up to 80% of its tumor volume), composed of a very fibrotic extracellular matrix, and of immune and non-immune stromal cells, of which cancer-associated fibroblasts (CAFs) are the majority. My research team is specifically interested in the role of CAFs in the aggressiveness of pancreatic cancer cells, with the objective of understanding the biology of CAFs, their dialogues with cancer cells and with other stromal cells (endothelial and immune), and how these dialogues impact the resistance of cancer cells to chemotherapies or immunotherapies. The understanding of these inter-cellular dialogues and with the extracellular matrix allows us to propose and test anti-cancer therapies co-targeting cancer cells and their stroma, in particular by targeted nanotherapies approaches (Veronique Gigoux’s project).

Thus, to understand the tumor-stroma dialogues correlated with the aggressiveness of pancreatic cancer, our team is i/ developing models integrating this stroma and mimicking the pathology in the patient, such as PDX (Patient-Derived Xenografts) and primocultures of CAFs and tumor cells grown in 3 dimensions (tumor organoids) and in co-culture with CAFs, as well as murine pancreatic cancer models (genetically modified mice developing spontaneous cancer, and orthotopic surgical transplantation of pancreatic cancer cells with CAFs) ; and ii/ performings separate analyses of gene expression in the tumor epithelial compartment and in the stromal compartment, using transcriptomics (mRNA expression), translactomics (translated RNA expression, project of Yvan Martineau), and matrisome (exhaustive analysis of matrix proteins expression, Christine Jean’s project) on PDX (hybrid grafted tumor models) naïve to treatment or rendered chemoresistant (Corinne Bousquet’s project), and/or by bioinformatics deconvolution on bulk RNAseq of human tumors.

Tumor organoid (left: immunofluorescence to visualize the cytokeratin cytoskeleton in green, the actin filaments particularly abundant at the brush border in pink and the nuclei in blue; right: transmission electron microscopy).

Pancreatic cancer

Microenvironment & Cancer-Associated Fibroblasts



Translational regulation

Metabolic reprogramming

Matrix rigidity & mechano-transduction

Patient-derived experimental models

Targeted nanotherapies

(polysome) RNAseq & bioinformatics


Multiplexed tissue imaging




Rapetti-Mauss, Raphael, Jérémy Nigri, Camille Berenguier, Pascal Finetti, Sarah Simha Tubiana, Bonnie Labrum, Benoit Allegrini, et al. “SK2 Channels Set a Signalling Hub Bolstering CAF-Triggered Tumourigenic Processes in Pancreatic Cancer.” Gut 72, no. 4 (April 2023): 722–35.
Solorzano, Jacobo, Enrique Carrillo-de Santa Pau, Teresa Laguna, and Ana Busturia. “A Genome-Wide Computational Approach to Define MicroRNA-Polycomb/Trithorax Gene Regulatory Circuits in Drosophila.” Developmental Biology 495 (March 2023): 63–75.
Muzzolini, Milena, Ismahane Belhabib, Victoire Cardot, Annemilaï Tijeras-Raballand, Cindy Neuzillet, Corinne Bousquet, Renato Micelli Lupinacci, and Christine Jean. “Pancreatic Cancer Orthotopic Graft in a Murine Model.” Acta Cirurgica Brasileira 38 (2023): e382823.
Neuzillet, Cindy, Rémy Nicolle, Jérôme Raffenne, Annemilaï Tijeras-Raballand, Alexia Brunel, Lucile Astorgues-Xerri, Sophie Vacher, et al. “Periostin- and Podoplanin-Positive Cancer-Associated Fibroblast Subtypes Cooperate to Shape the Inflamed Tumor Microenvironment in Aggressive Pancreatic Adenocarcinoma.” The Journal of Pathology 258, no. 4 (December 2022): 408–25.
Shin, Sauyeun, Jacobo Solorzano, Mehdi Liauzun, Stéphane Pyronnet, Corinne Bousquet, and Yvan Martineau. “Translational Alterations in Pancreatic Cancer: A Central Role for the Integrated Stress Response.” NAR Cancer 4, no. 4 (December 2022): zcac031.
Sánchez-Morales, Adrià, Véronique Gigoux, Minos-Timotheos Matsoukas, Laura Perez-Benito, Daniel Fourmy, Ramón Alibes, Félix Busqué, Arnau Cordomí, and Jean-Marc Devaud. “Reduction of Stress Responses in Honey Bees by Synthetic Ligands Targeting an Allatostatin Receptor.” Scientific Reports 12, no. 1 (October 6, 2022): 16760.
Ponzo, Matteo, Anais Debesset, Mélissande Cossutta, Mounira Chalabi-Dchar, Claire Houppe, Caroline Pilon, Alba Nicolas-Boluda, et al. “Nucleolin Therapeutic Targeting Decreases Pancreatic Cancer Immunosuppression.” Cancers 14, no. 17 (August 31, 2022): 4265.
Alexander, Stephen Ph, Arthur Christopoulos, Anthony P. Davenport, Eamonn Kelly, Alistair Mathie, John A. Peters, Emma L. Veale, et al. “THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G Protein-Coupled Receptors.” British Journal of Pharmacology 178 Suppl 1 (October 2021): S27–156.
Belhabib, Ismahane, Sonia Zaghdoudi, Claire Lac, Corinne Bousquet, and Christine Jean. “Extracellular Matrices and Cancer-Associated Fibroblasts: Targets for Cancer Diagnosis and Therapy?” Cancers 13, no. 14 (July 11, 2021): 3466.
Alard, Amandine, Manon Strehaïano, David Müller, Charline Lasfargues, Stéphanie Cassant-Sourdy, Christine Jean, Corinne Bousquet, Yvan Martineau, and Stéphane Pyronnet. “Phosphorylation of the MNK1 Substrate EIF4E Is Not Required for Response to Acute Pancreatitis.” Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.] 21, no. 4 (June 2021): 677–81.
Samain, Rémi, Alexia Brunel, Thibault Douché, Marjorie Fanjul, Stéphanie Cassant-Sourdy, Julia Rochotte, Jérôme Cros, et al. “Pharmacologic Normalization of Pancreatic Cancer-Associated Fibroblast Secretome Impairs Prometastatic Cross-Talk With Macrophages.” Cellular and Molecular Gastroenterology and Hepatology 11, no. 5 (2021): 1405–36.
Hilmi, Marc, Rémy Nicolle, Corinne Bousquet, and Cindy Neuzillet. “Cancer-Associated Fibroblasts: Accomplices in the Tumor Immune Evasion.” Cancers 12, no. 10 (October 14, 2020): 2969.
Zaghdoudi, Sonia, Emilie Decaup, Ismahane Belhabib, Rémi Samain, Stéphanie Cassant‐Sourdy, Julia Rochotte, Alexia Brunel, et al. “Activity in Cancer‐associated Fibroblasts Is a Prognostic Marker and a Druggable Key Metastatic Player in Pancreatic Cancer.” EMBO Molecular Medicine, October 7, 2020.
Müller, David, Sauyeun Shin, Théo Goullet de Rugy, Rémi Samain, Romain Baer, Manon Strehaiano, Laia Masvidal-Sanz, et al. “EIF4A Inhibition Circumvents Uncontrolled DNA Replication Mediated by 4E-BP1 Loss in Pancreatic Cancer.” JCI Insight 4, no. 21 (November 1, 2019).
Laplagne, Chloé, Marcin Domagala, Augustin Le Naour, Christophe Quemerais, Dimitri Hamel, Jean-Jacques Fournié, Bettina Couderc, Corinne Bousquet, Audrey Ferrand, and Mary Poupot. “Latest Advances in Targeting the Tumor Microenvironment for Tumor Suppression.” International Journal of Molecular Sciences 20, no. 19 (September 23, 2019).
Saponaro, Chiara, Valéry Gmyr, Julien Thévenet, Ericka Moerman, Nathalie Delalleau, Gianni Pasquetti, Anais Coddeville, et al. “The GLP1R Agonist Liraglutide Reduces Hyperglucagonemia Induced by the SGLT2 Inhibitor Dapagliflozin via Somatostatin Release.” Cell Reports 28, no. 6 (August 6, 2019): 1447-1454.e4.
Neuzillet, Cindy, Annemilaï Tijeras-Raballand, Chanthirika Ragulan, Jérôme Cros, Yatish Patil, Matthieu Martinet, Mert Erkan, et al. “Inter- and Intra-Tumoural Heterogeneity in Cancer-Associated Fibroblasts of Human Pancreatic Ductal Adenocarcinoma.” The Journal of Pathology 248, no. 1 (May 2019): 51–65.
Goehrig, Delphine, Jérémy Nigri, Rémi Samain, Zhichong Wu, Paola Cappello, Gaëlle Gabiane, Xinyi Zhang, et al. “Stromal Protein Βig-H3 Reprogrammes Tumour Microenvironment in Pancreatic Cancer.” Gut 68, no. 4 (2019): 693–707.
Alard, Amandine, Catherine Marboeuf, Bertrand Fabre, Christine Jean, Yvan Martineau, Frédéric Lopez, Patrice Vende, et al. “Differential Regulation of the Three Eukaryotic MRNA Translation Initiation Factor (EIF) 4Gs by the Proteasome.” Frontiers in Genetics 10 (2019): 254.

team members

Pauline Thomas
Chercheur Post-Doctorant / Post-Doc researcher
Charline Ogier
Chercheur Post-Doctorant / Post-Doc researcher
Maxime Boyer
Ingénieur de laboratoire / laboratory engineer
Cédric Fabre
Master / Master student
Morgane Le Bras
Ingénieur de laboratoire / laboratory engineer
Petnoi Petsophonsakul
Ingénieur de laboratoire / laboratory engineer
Evangelia Papadopoulou
Doctorant / PhD student
Ludmila Recoules
Chercheur Post-Doctorant / Post-Doc researcher
Delphine Vezzosi
Hospitalo-Universitaire / University teacher hospital practitioner
Pascal Clerc
Ingénieur de laboratoire / laboratory engineer
Mehdi Liauzun
Doctorant / PhD student
Marjorie Fanjul
Enseignant chercheur / University researcher
Jacobo Solorzano
Doctorant / PhD student
Veronique Gigoux
Chercheur statutaire / permanent scientist
Ahmed Abdelhamid
Doctorant / PhD student
Hippolyte Audureau
Doctorant / PhD student
Justine Journaux
Doctorant / PhD student
Loubna Laib
Chercheur Post-Doctorant / Post-Doc researcher
Corinne Bousquet
Chercheur statutaire / permanent scientist
Yvan Martineau
Chercheur statutaire / permanent scientist

parternships & FUNDING

Centre de Recherches en Cancérologie de Toulouse

Centre de Recherches en Cancérologie de Toulouse (Oncopole)

Toulouse – FR

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05 82 74 15 75

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