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Krt5 + /Krt15 + foregut basal progenitors give rise to cyclooxygenase-2-dependent tumours in response to gastric acid stress.
- Source :
-
Nature communications [Nat Commun] 2019 May 20; Vol. 10 (1), pp. 2225. Date of Electronic Publication: 2019 May 20. - Publication Year :
- 2019
-
Abstract
- The effective prevention of tumor initiation, especially for potentially inoperable tumors, will be beneficial to obtain an overall higher quality of our health and life. Hence, thorough understanding of the pathophysiological mechanisms of early tumor formation arising from identifiable cellular origins is required to develop efficient preventative and early treatment options for each tumor type. Here, using genetically engineered mouse models, we provide preclinical experimental evidence for a long-standing open question regarding the pathophysiological potential of a microenvironmental and physiological stressor in tumor development, gastric acid-mediated regional microscopic injury in foregut squamous epithelia. This study demonstrates the association of gastric acid stress with Cyclooxygenase-2-dependent tumor formation originating from tumor-competent Krt5 <superscript>+</superscript> /Krt15 <superscript>+</superscript> foregut basal progenitor cells. Our findings suggest that clinical management of microenvironmental stressor-mediated microscopic injury may be important in delaying tumor initiation from foregut basal progenitor cells expressing pre-existing tumorigenic mutation(s) and genetic alteration(s).
- Subjects :
- Animals
Cell Differentiation drug effects
Digestive System pathology
Epithelial Cells pathology
Epithelium pathology
Gastrointestinal Neoplasms etiology
Keratin-15 genetics
Keratin-15 metabolism
Keratin-5 genetics
Keratin-5 metabolism
Mice
Mice, Transgenic
Neoplasms, Experimental etiology
Neoplasms, Experimental pathology
Proton Pump Inhibitors pharmacology
Stress, Physiological drug effects
Tumor Microenvironment
Carcinogenesis pathology
Cyclooxygenase 2 metabolism
Gastric Acid metabolism
Gastrointestinal Neoplasms pathology
Stem Cells pathology
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 31110179
- Full Text :
- https://doi.org/10.1038/s41467-019-10194-0