Giraud J, Seeneevassen L, Rousseau B, Bouriez D, Sifré E, Giese A, Nguyen TL, Tiffon C, Lippi Y, Azzi-Martin L, Pannequin J, Ménard A, Bessède E, Staedel C, Mégraud F, Belleannée G, Lehours P, Gronnier C, Dubus P, Varon C.
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.
KEYWORDS
CD44 variant; Cancer stem cells; Epithelial-mesenchymal transition; Gastric cancer; Metastasis initiating cells.
Giraud J, Seeneevassen L, Rousseau B, Bouriez D, Sifré E, Giese A, Nguyen TL, Tiffon C, Lippi Y, Azzi-Martin L, Pannequin J, Ménard A, Bessède E, Staedel C, Mégraud F, Belleannée G, Lehours P, Gronnier C, Dubus P, Varon C. CD44v3 is a marker of invasive cancer stem cells driving metastasis in gastric carcinoma. Gastric Cancer. 2023 Mar;26(2):234-249. doi: 10.1007/s10120-022-01357-y. Epub 2022 Dec 18. PMID: 36528833; PMCID: PMC9950191.
