Prognostic impact of CD44-positive cancer stem-like cells at the invasive front of gastric cancer

Abstract

Background:The invasive tumour front may provide prognostic information. We examined the relationship between the presence of cancer stem cells (CSCs) at the invasive tumour front and prognosis in gastric cancer (GC).Methods:CD44 is a CSC marker; accordingly, CD44 standard (CD44s), CD44 variant-6 (CD44v6), and CD44 variant-9 (CD44v9) expression were examined in 123 resected primary GCs and the clinical significance of CSCs at the invasive tumour front was analysed.Results:Thirteen (10.6%), 79 (64.2%), and 47 (38.2%) GCs were CD44s-, CD44v6-, and CD44v9-positive, respectively. Patients with CD44-positive expression at the invasive tumour front had significantly poorer disease-specific survival than those with negative expression (CD44s: P<0.00001, CD44v6: P=0.013, CD44v9: P=0.0002). CD44s expression at the invasive tumour front was an independent prognostic factor in resectable GC patients (hazard ratio=3.13; 95% confidence interval, 1.09–9.01; P=0.035) and was significantly associated with peritoneal (P<0.001), lymphatic (P<0.001), and haematogenous recurrences (P=0.008). In addition, the number of CD44 isoforms expressed in cancer cells at the invasive tumour front was associated with patient prognosis. No conventional clinicopathological factors were independently associated with CD44 expression at the invasive tumour front.Conclusions:CD44-positive cancer stem-like cells at the invasive tumour front indicate poor survival and can be a unique biological prognostic factor for GC.

Multifunctional, CD44v6-Targeted ORMOSIL Nanoparticles Enhance Drugs Toxicity in Cancer Cells

“…In the case of the antibody-conjugated NPs, however, an inverse trend was observed, with NPs conjugated with a smaller amount of targeting agent being more effective than the ones conjugated with a larger amount of antibody. This observation is quite relevant as it confirms earlier observations that small amounts of antibodies are sufficient to obtain a good targeting and delivery efficiency [34,35]. When the density of antibody on the particles surface is increased, they may interfere with each other, decreasing their effectiveness.…”

“…One of the most known markers of CSCs is the CD44v6 isoform, and its metastasis promoting activity was first described in 1991 [32]. The CD44v6 isoform is overexpressed in several CSCs (e.g., in colorectal and pancreatic cancers [33], gastric cancer [34], and ovarian cancer [35]), thus representing an ideal candidate for targeted cancer therapies.Moreover, CD44 is the major hyaluronan receptor [36,37]. Hyaluronic acid (HA) is a natural, biodegradable, non-immunogenic, and water-soluble polysaccharide present in the extracellular matrix and synovial fluids [38][39][40][41].…”

“…One of the most known markers of CSCs is the CD44v6 isoform, and its metastasis promoting activity was first described in 1991 [32]. The CD44v6 isoform is overexpressed in several CSCs (e.g., in colorectal and pancreatic cancers [33], gastric cancer [34], and ovarian cancer [35]), thus representing an ideal candidate for targeted cancer therapies.…”

CD44v9 is associated with epithelial‐mesenchymal transition and poor outcomes in esophageal squamous cell carcinoma

“…CD44v9 expression is significantly associated with poor prognosis of patients with gastric, bladder, and liver cancers, as well as other cancers . Although most studies of CD44v9 examined its expression according to the intensity of staining or the proportion of CD44v9‐positive cells in whole tumor sections, several studies have reported levels of CD44v9 expression at the TIF . For example, in non‐muscle invasive bladder cancer expression of CD44v9 is localized to the TIF .…”

“…For example, in non‐muscle invasive bladder cancer expression of CD44v9 is localized to the TIF . In gastric cancer, expression of CD44v6 and CD44v9 at the TIF is more strongly associated with poor prognosis than expression in whole tumor sections …”