Comprehensive Profiling of Early Neoplastic Gastric Microenvironment Modifications and Biodynamics in Impaired BMP-Signaling FoxL1 + -Telocytes

• Published in: Biomedicines Vol. 11; no. 1; p. 19
• Main Authors: Alfonso, Alain B, Pomerleau, Véronique, Nicolás, Vilcy Reyes, Raisch, Jennifer, Jurkovic, Carla-Marie, Boisvert, François-Michel, Perreault, Nathalie
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.12.2022; MDPI
• Subjects: BMP signaling; Bone morphogenetic proteins; Cell interactions; Cell signaling; Cytokines; Epithelial cells; epithelial–mesenchymal interaction; Epithelium; Extracellular matrix; FoxL1+-telocytes; Gastric cancer; Glycoproteins; Growth factors; Homeostasis; Life sciences; Mass spectrometry; matrisome; mechanical microenvironment; Mesenchyme; Microenvironments; Peptides; Proteins; Proteomics; Scientific imaging; United States > US; BMP signaling; mechanical microenvironment; matrisome; epithelial–mesenchymal interaction; extracellular matrix; FoxL1+-telocytes
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines11010019

FoxL1 telocytes (TC ) are novel gastrointestinal subepithelial cells that form a communication axis between the mesenchyme and epithelium. TC 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 TC 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 gastric neoplasia linked to TC dysregulation has never been performed. This study provides a better understanding of how TC defective BMP signaling participates in the gastric pre-neoplastic microenvironment. Using a proteomic approach, we determined the changes in the complete matrisome of 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 fraction of gastric tissues microenvironment. These results show that TC 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.