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

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.

PHD finger protein 10 promotes cell proliferation by regulating CD44 transcription in gastric cancer

“…It is very likely that they regulate the same genes by forming the same SWI/SNF complex. Among them, we found that CD44 might be a good candidate since the latter was a well-known target of the SWI/SNF complex [ 28 ] and a proven marker of gastric cancer stem cells (GCSCs) [ 29 , 30 ], associated with proliferation of gastric epithelial cells [ 31 ]. Furthermore, CD44 was also known to be closely related to cell invasiveness and poor prognosis of GC [ 32 ].…”

From mechanism to therapy: the journey of CD24 in cancer

“…CD44 plays a crucial role in the resistance of CSCs to conventional therapies since it interacts with various components of the cell microenvironment, affecting cell adhesion, migration, and signaling pathways (167,169). Recent research has discovered that CD44v3 could be used as a marker of invasive cancer stem cells driving metastasis in gastric carcinoma (170). CD133 plays a pivotal role in the self-renewal capability of CSCs which maintaining their population within the tumor (171).…”

The Hyaluronan/CD44 Axis: A Double-Edged Sword in Cancer

“…Similarly, a meta-analysis assessing the prognostic significance of cancer stem cell markers in ovarian cancer from 52 studies concluded that CD44 correlated with worse disease-free survival, as well as with chemotherapy resistance [62].…”