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- Title
CD44v3 is a marker of invasive cancer stem cells driving metastasis in gastric carcinoma.
- Authors
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
- Abstract
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.
- Subjects
CANCER stem cells; CANCER invasiveness; STOMACH cancer; TUMOR markers; PRECANCEROUS conditions
- Publication
Gastric Cancer, 2023, Vol 26, Issue 2, p234
- ISSN
1436-3291
- Publication type
Article
- DOI
10.1007/s10120-022-01357-y