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Article Dans Une Revue Gastric Cancer Année : 2023

CD44v3 is a marker of invasive cancer stem cells driving metastasis in gastric carcinoma

Julie Pannequin

Résumé

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.
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hal-03908191 , version 1 (20-12-2022)

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Paternité

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Julie Giraud, Lornella Seeneevassen, Benoit Rousseau, Damien Bouriez, Elodie Sifré, et al.. CD44v3 is a marker of invasive cancer stem cells driving metastasis in gastric carcinoma. Gastric Cancer, inPress, 26 (2), pp.234-249. ⟨10.1007/s10120-022-01357-y⟩. ⟨hal-03908191⟩
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