Nature communications, 2020-01, Vol.11 (1), p.84-13, Article 84
2020
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- Autor(en) / Beteiligte
- Titel
- Gastric squamous-columnar junction contains a large pool of cancer-prone immature osteopontin responsive Lgr5 - CD44 + cells
- Ist Teil von
- Nature communications, 2020-01, Vol.11 (1), p.84-13, Article 84
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2020
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Areas of a junction between two types of epithelia are known to be cancer-prone in many organ systems. However, mechanisms for preferential malignant transformation at the junction areas remain insufficiently elucidated. Here we report that inactivation of tumor suppressor genes Trp53 and Rb1 in the gastric squamous-columnar junction (SCJ) epithelium results in preferential formation of metastatic poorly differentiated neoplasms, which are similar to human gastroesophageal carcinoma. Unlike transformation-resistant antral cells, SCJ cells contain a highly proliferative pool of immature Lgr5 CD44 cells, which are prone to transformation in organoid assays, comprise early dysplastic lesions, and constitute up to 30% of all neoplastic cells. CD44 ligand osteopontin (OPN) is preferentially expressed in and promotes organoid formation ability and transformation of the SCJ glandular epithelium. OPN and CD44 overexpression correlate with the worst prognosis of human gastroesophageal carcinoma. Thus, detection and selective targeting of the active OPN-CD44 pathway may have direct clinical relevance.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2041-1723eISSN: 2041-1723DOI: 10.1038/s41467-019-13847-2Titel-ID: cdi_doaj_primary_oai_doaj_org_article_cc9b087fae6a467297a9cdf23f9d6ec2
- Format
- –
- Schlagworte
- Aged, Aged, 80 and over, Animals, Biomedical materials, Cancer, Carcinoma, Squamous Cell - genetics, Carcinoma, Squamous Cell - metabolism, Carcinoma, Squamous Cell - mortality, Carcinoma, Squamous Cell - pathology, CD44 antigen, Cell Transformation, Neoplastic, Cohort Studies, Deactivation, Epithelium, Esophagogastric Junction - metabolism, Esophagogastric Junction - pathology, Esophagus, Female, Gastric cancer, Genetic transformation, Humans, Hyaluronan Receptors - genetics, Hyaluronan Receptors - metabolism, Inactivation, Male, Medical prognosis, Metastases, Metastasis, Mice, Mice, Knockout, Middle Aged, Mutation, Neoplasia, Neoplasms, Organoids, Osteopontin, Osteopontin - genetics, Osteopontin - metabolism, Ovaries, Receptors, G-Protein-Coupled - genetics, Receptors, G-Protein-Coupled - metabolism, Retinoblastoma Protein - genetics, Retinoblastoma Protein - metabolism, Stem cells, Stomach Neoplasms - genetics, Stomach Neoplasms - metabolism, Stomach Neoplasms - mortality, Stomach Neoplasms - pathology, Transformations, Tumor suppressor genes, Tumor Suppressor Protein p53 - genetics, Tumor Suppressor Protein p53 - metabolism, Tumors