| Autor: |
Giraud, Julie, Seeneevassen, Lornella, Rousseau, Benoit, Bouriez, Damien, Sifré, Elodie, Giese, Alban, Nguyen, Tra Ly, Tiffon, Camille, Lippi, Yannick, Azzi-Martin, Lamia, Pannequin, Julie, Ménard, Armelle, Bessède, Emilie, Staedel, Cathy, Mégraud, Francis, Belleannée, Geneviève, Lehours, Philippe, Gronnier, Caroline, Dubus, Pierre, Varon, Christine |
| Předmět: |
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| Zdroj: |
Gastric Cancer; Mar2023, Vol. 26 Issue 2, p234-249, 16p |
| Abstrakt: |
Background: Cancer stem cells (CSCs) are at the origin of tumour initiation and progression in gastric adenocarcinoma (GC). However, markers of metastasis-initiating cells remain unidentified in GC. In this study, we characterized CD44 variants expressed in GC and evaluated the tumorigenic and metastatic properties of CD44v3+ cells and their clinical significance in GC patients. Methods: Using GC cell lines and patient-derived xenografts, we evaluated CD44+ and CD44v3+ GC cells molecular signature and their tumorigenic, chemoresistance, invasive and metastatic properties, and expression in patients-derived tissues. Results: CD44v3+ cells, which represented a subpopulation of CD44+ cells, were detected in advanced preneoplastic lesions and presented CSCs chemoresistance and tumorigenic properties in vitro and in vivo. Molecular and functional analyses revealed two subpopulations of gastric CSCs: CD44v3+ CSCs with an epithelial-mesenchymal transition (EMT)-like signature, and CD44+/v3– CSCs with an epithelial-like signature; both were tumorigenic but CD44v3+ cells showed higher invasive and metastatic properties in vivo. CD44v3+ cells detected in the primary tumours of GC patients were associated with a worse prognosis. Conclusion: CD44v3 is a marker of a subpopulation of CSCs with metastatic properties in GC. The identification of metastasis-initiating cells in GC represents a major advance for further development of anti-metastatic therapeutic strategies. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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