Comprehensive Profiling of early Neoplastic Gastric Microen-vironment Modifications and Biodynamics in Impaired BMP-Signaling Foxl1+-Telocytes

ABSTRACT: FoxL1+telocytes (TCFoxL1+) are novel gastrointestinal subepithelial cells that form communication axis between the mesenchyme and epithelium. TCFoxL1+ are strategically positioned to be key contributors to the microenvironment through production and secretion of growth factors and extracellular matrix (ECM) proteins. In recent years, the alteration of the bone morphogenetic protein (BMP) signaling in TCFoxL1+ was demonstrated to trigger a toxic microenvironment with ECM remodeling that leads to the development of pre-neoplastic gastric lesions. However, a comprehensive analysis of variations in the ECM composition and its associated proteins in gas-tric neoplasia linked to TCFoxL1+ dysregulation has never been performed. This study provides a better understanding of how TCFoxL1+ defective BMP signaling participates in gastric pre-neoplastic microenvironment. Using a proteomic approach, we determined the changes in the complete matrisome of BmpR1a△FoxL1+ and control mice, both in total antrum as well as in isolated mesenchyme-enriched antrum fractions. Comparative proteomic analysis revealed that the deconstruction of the gastric antrum led to a more comprehensive analysis of the ECM frac-tion of gastric tissues microenvironment. These results show that TCFoxL1+ are key members of the mesenchymal cell population and actively participate in the establishment of the matrisomic fraction of the microenvironment; thus, influencing epithelial cell behavior

INSTRUMENT(S): timsTOF

ORGANISM(S): Mus Musculus (mouse)

DISEASE(S): Disease Free

SUBMITTER: Dominique Levesque  

LAB HEAD: Nathalie Perreault

PROVIDER: PXD038603 | Pride | 2023-03-11

REPOSITORIES: Pride