Cancer stem cell markers CD133 and CD24 correlate with invasiveness and differentiation in colorectal adenocarcinoma.

Department of Pathology, College of Medicine, Hanyang University, Seoul, South Korea.
World Journal of Gastroenterology (Impact Factor: 2.37). 06/2009; 15(18):2258-64.
Source: PubMed


To verify that CD markers are available for detecting cancer stem cell populations and to evaluate their clinical significance in colon cancer.
Immunohistochemistry for CD133, CD24 and CD44 was performed on the tissue microarray of 523 colorectal adenocarcinomas. Medical records were reviewed and clinicopathological analysis was performed.
In colorectal adenocarcinoma, 128 of 523 cases (24.5%) were positive and 395 cases (75.5%) were negative for CD133 expression. Two hundred and sixty-four of 523 cases (50.5%) were positive and 259 cases (49.5%) were negative for CD24 expression. Five hundred and two of 523 cases (96%) were negative and 21 cases (4%) were positive for CD44 expression. Upon clinicopathological analysis, CD133 expression was present more in male patients (P = 0.002) and in advanced T stage cancer (P = 0.024). Correlation between CD24 expression and clinicopathological factors was seen in the degree of differentiation (P = 0.006). Correlation between CD44 expression and clinicopathological factors was seen in the tumor size (P = 0.001). Survival was not significantly related to CD133, CD24 and CD44 expression.
CD markers were related to invasiveness and differentiation of colorectal adenocarcinoma. However, CD expression was not closely related to survival.

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Available from: Kyung Yul Hur, May 28, 2015
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    • "Similarly, a CD24+/CD44+ cancer stem cell subpopulation has been identified in solid tumors and cancer cell lines in both colorectal and ovarian cancers [8,9]. CD24 has been shown to be related to invasiveness and differentiation of colorectal adenocarcinoma [34]. CD24 has also been identified as one of the cancer stem cell markers in human malignant mesothelioma cells [35]. "
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    ABSTRACT: Current evidence suggests that initiation, growth, and invasion of cancer are driven by a small population of cancer stem cells (CSC). Previous studies have identified CD44+ cells as cancer stem cells in head and neck squamous cell carcinoma (HNSCC). However, CD44 is widely expressed in most cells in HNSCC tumor samples and several cell lines tested. We previously identified a small population of CD24+/CD44+ cells in HNSCC. In this study, we examined whether this population of cells may represent CSC in HNSCC. CD24+/CD44+ cells from HNSCC cell lines were sorted by flow cytometry, and their phenotype was confirmed by qRT-PCR. Their self-renewal and differentiation properties, clonogenicity in collagen gels, and response to anticancer drugs were tested in vitro. The tumorigenicity potential of CD24+/CD44+ cells was tested in athymic nude mice in vivo. Our results show that CD24+/CD44+ cells possessed stemness characteristics of self-renewal and differentiation. CD24+/CD44+ cells showed higher cell invasion in vitro and made higher number of colonies in collagen gels compared to CD24-/CD44+ HNSCC cells. In addition, the CD24+/CD44+ cells were more chemo-resistant to gemcitabine and cisplatin compared to CD24-/CD44+ cells. In vivo, CD24+/CD44+ cells showed a tendency to generate larger tumors in nude mice compared to CD24-/CD44+ cell population. Our study clearly demonstrates that a distinct small population of CD24+/CD44+ cells is present in HNSCC that shows stem cell-like properties. This distinct small population of cells should be further characterized and may provide an opportunity to target HNSCC CSC for therapy.
    BMC Cancer 03/2014; 14(1):173. DOI:10.1186/1471-2407-14-173 · 3.36 Impact Factor
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    • "CSCs represent a novel target for drug discovery for cancer; however, the mechanisms that regulate the self-renewal and multipotency of CSCs remain unclear. It has been suggested that CD44 [8], CD24 [7], and CD133 [9] are hallmarks for colon cancer stem cells (CCSCs). In this study, cell surface markers CD44 and CD24 were thus used to select CCSCs from human colorectal cancer cell lines. "
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    ABSTRACT: Colorectal cancer is one of the most common and fatal tumors. However, molecular mechanisms underlying carcinogenesis of colorectal cancer remain largely undefined. Here, we explored the expression and function of Nodal in colon cancer stem cells (CCSCs). Nodal and its receptors were present in numerous human colorectal cancer cell lines. NODAL and ALK-4 were coexpressed in human colon cancerous tissues, and NODAL, CD24, and CD44, markers for CCSCs, were expressed at higher levels in human colon cancerous tissues than adjacent noncancerous colon tissues. Human CCSCs were isolated by magnetic activated cell sorting using anti-CD24 and anti-CD44. Nodal transcript and protein were hardly detectable in CD44- or CD24-negative human colorectal cancer cell lines, whereas Nodal and its receptors were present in CCSCs. Notably, Nodal facilitated spheroid formation of human CCSCs, and phosphorylation of Smad2 and Smad3 was activated by Nodal in cells of spheres derived from human CCSCs. Collectively, these results suggest that Nodal promotes the self-renewal of human CCSCs and mediate carcinogenesis of human colorectal cancer via an autocrine manner through Smad2/3 pathway. This study provides a novel insight into molecular mechanisms controlling fate of human CCSCs and offers new targets for gene therapy of human colorectal cancer.
    02/2014; 2014:364134. DOI:10.1155/2014/364134
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    • "Besides CD44, a number of CD markers have been identified as cancer stem cell markers in several solid tumors. The glycoprotein CD133, also known as prominin1, is a stem cell surface antigen in brain, colorectal, and prostate cancer [15]. Another cell surface marker is the single-chain sialoglycoprotein CD24, which is associated with cancer stem cell characteristics in colorectal and pancreatic cancer, while head and neck cancer cells and breast cancer cells with CD44+CD24−/low expression are highly tumorigenic [16–18]. "
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    ABSTRACT: CD44 is a complex family of molecules, associated with aggressive malignancies and cancer stem cells. However, the role of CD44 variants in tumor progression and treatment resistance is not clear. In this study, the expression of CD44 and its variants was assessed in head and neck squamous cell carcinomas (HNSCC). Furthermore, subpopulations of cells expressing high amounts of CD44 variants were identified and characterized, for e.g., cell cycle phase and radioresistance. Results revealed high and homogenous CD44 and CD44v7 expression in four cell lines and CD44v4 and CD44v6 in three cell lines. CD44v3 was highly expressed in two cell lines, whereas CD44v5, CD44v7/8, CD44v10, CD133, and CD24 demonstrated no or moderate expression. Moreover, a subpopulation of very high CD44v4 expression was identified, which is independent of cell phase, demonstrating increased proliferation and radioresistance. In cell starvation experiments designed to enrich for cancer stem cells, a large population with dramatically increased expression of CD44, CD44v3, CD44v6, and CD44v7 was formed. Expression was independent of cell phase, and cells demonstrated increased radioresistance and migration rate. Our results demonstrate that the heterogeneity of tumor cells has important clinical implications for the treatment of HNSCC and that some of the CD44 variants may be associated with increased radioresistance. Highly expressed CD44 variants could make interesting candidates for selective cancer targeting.
    Tumor Biology 10/2013; 35(3). DOI:10.1007/s13277-013-1272-3 · 3.61 Impact Factor
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