Long-term Helicobacter pylori infection switches gastric epithelium reprogramming towards cancer stem cell-related differentiation program in Hp-activated gastric fibroblast-$TGF\beta$ dependent manner
| Autor: | Tomasz Brzozowski, Aneta Targosz, Gracjana Krzysiek-Maczka, Malgorzata Strzalka, Urszula Szczyrk, Jarosław Czyż, Agata Ptak-Belowska, Tomasz Wróbel |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Microbiology (medical) cancer stem cells Stromal cell cancer associated fibroblasts (CAFs) Chronic gastritis Microbiology Article 03 medical and health sciences 0302 clinical medicine Cancer stem cell Virology Gastric mucosa medicine Fibroblast epithelial–mesenchymal transition (EMT) lcsh:QH301-705.5 Helicobacter pylori Chemistry gastric cancer TGFβ1 LGR5 medicine.disease 030104 developmental biology medicine.anatomical_structure epithelial–myofibroblast transition lcsh:Biology (General) 030220 oncology & carcinogenesis embryonic structures Cancer research Reprogramming Gastric Neoplasm activated fibroblasts |
| Zdroj: | Microorganisms, Vol 8, Iss 1519, p 1519 (2020) Microorganisms Volume 8 Issue 10 |
| Popis: | Helicobacter pylori (Hp)-induced inflammatory reaction leads to a persistent disturbance of gastric mucosa and chronic gastritis evidenced by deregulation of tissue self-renewal and local fibrosis with the crucial role of epithelial&ndash mesenchymal transition (EMT) in this process. As we reported before, Hp activated gastric fibroblasts into cells possessing cancer-associated fibroblast properties (CAFs), which secreted factors responsible for EMT process initiation in normal gastric epithelial RGM1 cells. Here, we showed that the long-term incubation of RGM1 cells in the presence of Hp-activated gastric fibroblast (Hp-AGF) secretome induced their shift towards plastic LGR5+/Oct4high/Sox-2high/c-Mychigh/Klf4low phenotype (l.t.EMT+RGM1 cells), while Hp-non-infected gastric fibroblast (GF) secretome prompted a permanent epithelial&ndash myofibroblast transition (EMyoT) of RGM1 cells favoring LGR-/Oct4high/Sox2low/c-Myclow/Klf4high phenotype (l.t.EMT-RGM1 cells). TGF&beta 1 rich secretome from Hp-reprogrammed fibroblasts prompted phenotypic plasticity and EMT of gastric epithelium, inducing pro-neoplastic expansion of post-EMT cells in the presence of low TGF&beta R1 and TGF&beta R2 activity. In turn, TGF&beta R1 activity along with GF-induced TGF&beta R2 activation in l.t.EMT-RGM1 cells prompted their stromal phenotype. Collectively, our data show that infected and non-infected gastric fibroblast secretome induces alternative differentiation programs in gastric epithelium at least partially dependent on TGF&beta signaling. Hp infection-activated fibroblasts can switch gastric epithelium microevolution towards cancer stem cell-related differentiation program that can potentially initiate gastric neoplasm. |
| Databáze: | OpenAIRE |
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