Expression of POU2F3 Transcription Factor Control Inflammation, Immunological Recruitment and Metastasis of Pancreatic Cancer in Mice
Jennifer Bintz,
Analía Meilerman Abuelafia,
François Gerbe,
Elodie Baudoin,
Nathalie Auphan-Anezin,
Emmanuelle Sidot,
Philippe Jay,
Juan Iovanna
Affiliations
Jennifer Bintz
Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, 13288 Marseille, France
Analía Meilerman Abuelafia
Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, 13288 Marseille, France
François Gerbe
Institute of Functional Genomics (IGF), University of Montpellier, CNRS, INSERM, Equipe Labellisee Ligue Contre le Cancer, 34000 Montpellier, France
Elodie Baudoin
Centre d’Immunologie de Marseille-Luminy, Aix-Marseille Université, INSERM U1104, CNRS UMR 7280, Parc Scientifique et Technologique de Luminy, 13288 Marseille, France
Nathalie Auphan-Anezin
Centre d’Immunologie de Marseille-Luminy, Aix-Marseille Université, INSERM U1104, CNRS UMR 7280, Parc Scientifique et Technologique de Luminy, 13288 Marseille, France
Emmanuelle Sidot
Institute of Functional Genomics (IGF), University of Montpellier, CNRS, INSERM, Equipe Labellisee Ligue Contre le Cancer, 34000 Montpellier, France
Philippe Jay
Institute of Functional Genomics (IGF), University of Montpellier, CNRS, INSERM, Equipe Labellisee Ligue Contre le Cancer, 34000 Montpellier, France
Juan Iovanna
Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, 13288 Marseille, France
TUFT cells have been described as strong modulators of inflammatory cells in several tissues including pancreas. TUFT cells, also known as DCLK1+ cells, are dependent of the transcriptional factor POU2F3. Several works report DCLK1+ cells in early stages of PDAC development suggesting an important role of TUFT cells in PDAC development. Therefore, we developed a mice model (PDX1-Cre;KrasG12D;Ink4afl/fl), known as PKI model, deficient or not of POU2F3. In this animal model, deficiency of POU2F3 results in the absence of TUFT cells in PDAC as expected. Although, tumor development and growth are not significantly influenced, the development of liver metastasis was almost completely inhibited in POU2F3-deficient mice. Surprisingly, the absence of metastasis was associated with a higher expression of epithelial-to-mesenchymal transition markers, but to a lower inflammatory microenvironment suggesting that inflammation influences metastasis production more than epithelial-to-mesenchymal transition in this animal model. We can conclude that POU2F3 could be a new therapeutic target for control PDAC progression.
