CD24 Expression Is Increased in 5-Fluorouracil-Treated Esophageal Adenocarcinoma Cells

Abstract

The cancer stem cell (CSC) model suggests that there are subsets of cells within a tumor with increased proliferation and self-renewal capacity, which play a key role in therapeutic resistance. The importance of cyclooxygenase-2 (COX-2) in carcinogenesis has been previously established and the use of COX-2 inhibitors as celecoxib has been shown to exert antitumor effects. The present study investigated whether treatment of esophageal adenocarcinoma (EAC) cells with 5-fluorouracil (5-FU) or the growth of tumor spheres increased the proportion of CSCs and also if treatment with celecoxib was able to reduce the putative CSC markers in this tumor. OE19 and OE33 EAC cells surviving 5-FU exposure exhibited an increase in CSC markers CD24 and ABCG2 and also an increased resistance to apoptosis. EAC cell lines had the capacity to form multiple spheres displaying typical CSC functionalities such as self-renewal and increased CD24 levels. In addition, after the induction of differentiation, cancer cells reached levels of CD24 similar to those observed in the parental cells. Treatment with celecoxib alone or in combination with 5-FU also resulted in a reduction of CD24 expression. Moreover, celecoxib inhibited the growth of tumor spheres. These findings showing a reduction in CSC markers induced by celecoxib suggest that the COX-2 inhibitor might be a candidate for combined chemotherapy in the treatment of EAC. However, additional clinical and experimental studies are needed.

ABC Transporters and Their Role in the Neoadjuvant Treatment of Esophageal Cancer

“…Recently, OE19 and OE33 esophageal adenocarcinoma cell subpopulations surviving 5-fluorouracil treatment exhibited an increase in expression of cancer stem cell markers CD24 (600074) and ABCG2. These cells also exerted increased resistance to apoptosis [ 167 ]. Other members of ABC family have been shown related to stemness as well.…”

Advances in Drug Resistance of Esophageal Cancer: From the Perspective of Tumor Microenvironment

“…Like other cancers, the identification of esophageal CSCs is based on the specific expression of stemness-related surface markers, including CD24, CD44, CD90, CD133, CLDN4, EpCAM, OV6, and p75NTR, some of which are associated with drug resistance and have the potential to predict the therapeutic response ( Yamaguchi et al, 2016 ; Jiménez et al, 2017 ; Liu et al, 2017 ; Wang et al, 2017 ; Wang D. et al, 2019 ; Sun et al, 2018 ; Xu et al, 2018 ; Lin et al, 2019 ; Figure 1A ). p75NTR, also referred to as CD271, is a receptor of the neurotrophic growth factor family that mediates various cell outcomes, such as cell apoptosis during neurodevelopmental processes ( Barker, 2004 ).…”

CD24 is a Potential Biomarker for Prognosis in Human Breast Carcinoma

“…Previous studies have shown that abnormal overexpression of CD24 is an unfavorable prognostic factor during carcinogenesis in various neoplasms [10,15,23,27,28]. Meanwhile, CD24 can upregulate the activity of STAT3 and the expression of prototype STAT3-regulated genes [29].…”

“…Cluster of differentiation (CD) 24 is a small glycosyl phosphatidylinositol (GPI)-linked membrane glycoprotein (27)(28)(29)(30) amino acids in length) with glycosylation sites that bind P-selectin [7,8]. High expression levels of CD24 have been identified in various types of cancers-such as breast, prostate, pancreas, ovary, colorectal, and bladder cancers-and indicate poor prognosis [9][10][11][12].…”