癌干细胞(CSCs) 是胃腺癌 (GC) 肿瘤起始和发展的起源。然而，在GC中，转移起始细胞的标志仍未确定。在本研究中，我们表征了在GC中表达的CD44变体，并评估了CD44v3+细胞的肿瘤原性和转移性质及其在GC患者中的临床意义。使用GC细胞系和来自患者的异种移植，我们评估了CD44+和CD44v3+ GC细胞的分子特征、肿瘤原性、化疗抗性、侵袭和转移性质以及在患者源性组织中的表达。CD44v3+细胞是CD44+细胞的亚群，在晚期癌前病变中被检测到，并在体外和体内展示出CSCs化疗抗性和肿瘤性能。分子和功能分析揭示了两种胃CSCs的亚群：带有上皮-间充质转化(EMT)标志的CD44v3+ CSCs和带有上皮标志的CD44+/v3- CSCs；两者都有肿瘤原性，但CD44v3+细胞在体内显示出更高的侵袭性和转移性质。在GC患者的原发性肿瘤中检测到的CD44v3+细胞与不良预后相关。CD44v3是GC中具有转移性质的CSCs的标志。GC中转移起始细胞的确认为进一步开发抗转移疗法战略的重要进展。©2022作者（们）。

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.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.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.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.© 2022. The Author(s).