The Role of CD44 in the Pathogenesis, Diagnosis, and Therapy of Gastric Cancer

Abstract

CD44 is a transmembrane glycoprotein and surface receptor for hyaluronan that is involved in the response of cells to their microenvironment. CD44 splice variants play roles in carcinogenesis, differentiation, and lymph node metastasis and are predictive of the prognosis for various carcinomas, including gastric cancer. Current data suggest that gastric tissue stem cells and gastric cancer stem cells both express the splice variant, CD44v9. Overall, the data regarding the alterations that occur in CD44 and its splice variants in response to acute and chronic infection with Helicobacter pylori are scant and poorly elucidated in terms of possible changes in expression that occur in gastric cancer precursor lesions, such as chronic atrophic gastritis, pyloric metaplasia and intestinal metaplasia. In this study, we discuss the available data and suggest which new data would likely be useful in clinical practice. We also discuss the potential for CD44-targeted therapeutic strategies in gastric cancer. CD44 and its splice variants are positively associated with the initiation and progression of gastric cancer and may also play important roles in diagnosis, therapy and prognosis. CD44 research has been active but fragmented, and it may offer new therapeutic approaches to gastric cancer.

Inhibitory effect of ibuprofen on tumor survival and angiogenesis in gastric cancer cell

“…Both OCT4 and CD44 are the main markers of gastric cancer stem cells [21,22]. Therefore, reduction in the expression of these two genes may be due to reduction in the stemness characteristics of AGS cells.…”

Effectiveness of plasma treatment on gastric cancer cells

“…CD44 is essentially a major component of extracellular matrices and has some variant isoforms, which arise by the alternative splicing of variant exons. One of these variants, CD44v9, is considered as a candidate stem cell marker for gastric cancer [28], and is significantly associated with recurrence, mortality, and resistance to chemotherapy or radiotherapy [29][30][31] through its role as a common downstream effector of RAS [32]. More recently, the correlation between CD44v9 expression and resistance to ROS was reported [19].…”

Macrophage Migration Inhibitory Factor: a Potential Marker for Cancer Diagnosis and Therapy

“…CD44 is a co receptor of MIF which upon binding starts a downstream signaling pathway involving the ERK1/2 pathway and AKT pathway (Shi et al, 2006). It is speculated that CD44 plays a role in invasion and its being considered as a metastasis promoting molecule (Marhaba & Zoller, 2004;Jang et al, 2011). CD44 helps in the attachment of stem cells and circulation of the tumor cells to the bone marrow endothelial cells (Lapidot et al, 2005).…”