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Comparative study of the role of interepithelial mucosal mast cells in the context of intestinal adenoma-carcinoma progression

Mast cells (MCs) are crucial players in the relationship between the tumor microenvironment (TME) and cancer cells and have been shown to influence angiogenesis and progression of human colorectal cancer (CRC). However, the role of MCs in the TME is controversially discussed as either pro- or anti-t...

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Hauptverfasser: Groll, Tanja Maria (VerfasserIn) , Silva, Miguel (VerfasserIn) , Sarker, Rim Sabrina Jahan (VerfasserIn) , Tschurtschenthaler, Markus (VerfasserIn) , Schnalzger, Theresa (VerfasserIn) , Mogler, Carolin (VerfasserIn) , Denk, Daniela (VerfasserIn) , Schölch, Sebastian (VerfasserIn) , Schraml, Barbara U. (VerfasserIn) , Ruland, Jürgen Maximilian (VerfasserIn) , Rad, Roland (VerfasserIn) , Saur, Dieter (VerfasserIn) , Weichert, Wilko (VerfasserIn) , Jesinghaus, Moritz (VerfasserIn) , Matiasek, Kaspar (VerfasserIn) , Steiger, Katja (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 30 April 2022
In: Cancers
Year: 2022, Jahrgang: 14, Heft: 9, Pages: 1-23
ISSN:2072-6694
DOI:10.3390/cancers14092248
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/cancers14092248
Verlag, kostenfrei, Volltext: https://www.mdpi.com/2072-6694/14/9/2248
Volltext
Verfasserangaben:Tanja Groll, Miguel Silva, Rim Sabrina Jahan Sarker, Markus Tschurtschenthaler, Theresa Schnalzger, Carolin Mogler, Daniela Denk, Sebastian Schölch, Barbara U. Schraml, Jürgen Ruland, Roland Rad, Dieter Saur, Wilko Weichert, Moritz Jesinghaus, Kaspar Matiasek and Katja Steiger
Beschreibung
Zusammenfassung:Mast cells (MCs) are crucial players in the relationship between the tumor microenvironment (TME) and cancer cells and have been shown to influence angiogenesis and progression of human colorectal cancer (CRC). However, the role of MCs in the TME is controversially discussed as either pro- or anti-tumorigenic. Genetically engineered mouse models (GEMMs) are the most frequently used in vivo models for human CRC research. In the murine intestine there are at least three different MC subtypes: interepithelial mucosal mast cells (ieMMCs), lamina proprial mucosal mast cells (lpMMCs) and connective tissue mast cells (CTMCs). Interepithelial mucosal mast cells (ieMMCs) in (pre-)neoplastic intestinal formalin-fixed paraffin-embedded (FFPE) specimens of mouse models (total lesions n = 274) and human patients (n = 104) were immunohistochemically identified and semiquantitatively scored. Scores were analyzed along the adenoma-carcinoma sequence in humans and 12 GEMMs of small and large intestinal cancer. The presence of ieMMCs was a common finding in intestinal adenomas and carcinomas in mice and humans. The number of ieMMCs decreased in the course of colonic adenoma-carcinoma sequence in both species (p < 0.001). However, this dynamic cellular state was not observed for small intestinal murine tumors. Furthermore, ieMMC scores were higher in GEMMs with altered Wnt signaling (active β-catenin) than in GEMMs with altered MAPK signaling and wildtypes (WT). In conclusion, we hypothesize that, besides stromal MCs (lpMMCs/CTMCs), particularly the ieMMC subset is important for onset and progression of intestinal neoplasia and may interact with the adjacent neoplastic epithelial cells in dependence on the molecular environment. Moreover, our study indicates the need for adequate GEMMs for the investigation of the intestinal immunologic TME.
Beschreibung:Gesehen am 20.02.2024
Beschreibung:Online Resource
ISSN:2072-6694
DOI:10.3390/cancers14092248

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