Identification of stem-like cells and clinical significance of candidate stem cell markers in gastric cancer

Abstract

The existence of gastric cancer stem cells (CSCs) has not been definitively proven and specific cell surface markers for identifying gastric CSCs have largely not been identified. Our research aimed to isolate potential gastric CSCs and clarify their clinical significance, while defining markers for GCSC identification and verification. Here, we report that spheroid cells possess stem cell-like properties, and overexpress certain stem cell markers. CD133 or CD44-positive cells also exhibit properties of CSCs. The expression of Oct4, Sox2, Gli1, CD44, CD133, p-AKT, and p-ERK was significantly higher in metastatic lesions compared to that in primary lesions. Elevated expression of some of these proteins was correlated with a more aggressive phenotype and poorer prognosis, including Oct4, Sox2, Gli1, CD44, and p-ERK. Multivariate Cox proportional hazards model analysis showed that only CD44 is an independent factor. Knockdown of CD44 down-regulated the stem cell-like properties, which was accompanied by the down-regulation of p-ERK and Oct4. Oct4 overexpression could reverse the decreased CSCs properties induced by CD44 knockdown. Taken together, our research revealed that spheroid cell culture, and CD133 or CD44-labeled FACS methods can be used to isolate gastric CSCs. Some CSC markers have clinical significance in predicting the prognosis. CD44 is an independent prognostic factor and maintains the properties of CSCs in CD44-p-ERK-Oct4 positive feedback loop.

Antitumor activity and inhibitory effects on cancer stem cell-like properties of Adeno-associated virus (AAV) -mediated Bmi-1 interference driven by Bmi-1 promoter for gastric cancer

“…Consistent with our previous data [22] we found that Ad-Bmi-1i can downregulate phosphorylated-AKT (pAKT). Besides this, Bmi-1 downregulation also leads to downregulation of pmTOR and reduction of VEGF in SGC-7901 cells (Figure 5A).…”

Overexpression of the Transmembrane Protein IQGAP3 Is Associated with Poor Survival of Patients with Gastric Cancer

“…Previously, the Akt and Erk signaling pathways were shown to be essential for maintaining the pluripotency of stem cells [23, 24]. Moreover, gastric spheroid cells are known to overexpress multiple stem cell markers, including Oct4, Sox2, Gli1, CD44, CD133, pAkt, and pErk [22]. Taken together, these results suggest that the phosphorylation of Akt and Erk by IQGAP3 is involved in spheroid formation by GC cells.…”

“…CSCs are defined as a unique subpopulation of cells that possess self-renewal and differentiation potential, and that are generally responsible for tumor initiation, invasion, metastasis, and chemo-resistance [22]. Thus, CSC characterization can improve our understanding of carcinogenesis and help explain the frequency of treatment failure for GC.…”

MicroRNA-145 exerts tumor-suppressive and chemo-resistance lowering effects by targeting CD44 in gastric cancer

“…The protein is not only involved in cell-cell adhesion, cell-matrix interactions, and tumor survival, but also has been accepted as a CSC marker for gastric cancer in many studies[9]. CD44 expression is upregulated in advanced gastric lesions[10]. Depletion of CD44 inhibited the stem cell-like properties, which was accompanied by the downregulation of Oct4[10].…”