CD24 Expression Causes the Aquisition of Multiple Cellular Properties Associated with Tumor Growth and Metastasis

Department of Cell Biology, University of Groningen, Groningen, Groningen, Netherlands
Cancer Research (Impact Factor: 9.33). 01/2006; 65(23):10783-93. DOI: 10.1158/0008-5472.CAN-05-0619
Source: PubMed


The glycosylphosphatidylinositol-anchored membrane protein CD24 functions as an adhesion molecule for P-selectin and L1 and plays a role in B-cell development and neurogenesis. Over the last few years, a large body of literature has also implicated CD24 expression in tumorigenesis and progression. Here, we show that ectopic CD24 expression can be sufficient to promote tumor metastasis in experimental animals. By developing a doxycycline-inducible system for the expression of CD24 in breast cancer cells, we have also analyzed the cellular properties that CD24 expression influences. We found that CD24 expression increased tumor cell proliferation. Furthermore, in addition to promoting binding to P-selectin, CD24 expression also indirectly stimulated cell adhesion to fibronectin, collagens I and IV, and laminin through the activation of alpha3beta1 and alpha4beta1 integrin activity. Moreover, CD24 expression supported rapid cell spreading and strongly induced cell motility and invasion. CD24-induced proliferation and motility were integrin independent. Together, these observations implicate CD24 in the regulation of multiple cell properties of direct relevance to tumor growth and metastasis.

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    • "A large body of literature suggests a role for CD24 in tumorigenesis and tumor progression. CD24 expression causes the acquisition of multiple cellular properties associated with tumor growth and metastasis [19]. Recent studies have identified CD24 as a marker in cancer stem cells in several cancers, including pancreatic cancer [11], colorectal cancer-derived cell lines [8], and ovarian cancer [9]. "
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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.
    Full-text · Article · Mar 2014 · BMC Cancer
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    • "Cytoskeleton remolding is essential for controlling cell motility and cancer invasion [22]. Up-regulation of CD24 could increase actin cytoskeletal remolding dynamic and enhance contractile forces to facilitate cancer cell invasion [23,24]. Myosin light chains phosphorylated by MYLK increase its interaction with actin filaments, and promote cell protrusion and contraction [25]. "
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    ABSTRACT: MTA2 gene belongs to metastasis associated family, and is highly expressed in some solid tumors, including gastric cancer. Its biological function in gastric cancer is currently undefined. Metastasis-associated tumor gene family 2 (MTA2) and transcription factor specificity protein 1 (Sp1) expression were detected in 127 gastric cancer samples by immunohistochemistry staining. SGC-7901 and AGS gastric cancer cell lines transfected by MTA2 shRNA was used for biological function investigation. Binding and regulation activities of Sp1 on MTA2 promoter were investigated by chromatin immunoprecipitation and luciferase reporter gene. The expression rate of MTA2 in gastric cancer tissues was 55.9% (71/127), and its expression was closely related to the depth of tumor invasion, lymph nodes metastasis, and TNM staging. MTA2 knockdown in human SGC-7901 and AGS gastric cancer cells significantly inhibited migration and invasion in vitro, and disrupted structure of cytoskeleton. MTA2 knockdown also attenuated xenografts growth and lung metastasis in nude mice model. MTA2 expression was positively correlated with transcription factor Sp1 in gastric cancer tissues (r = 0.326, P < 0.001). Sp1 bound to human MTA2 gene promoter at region from -1043 bp to -843 bp. Transcriptional activity of MTA2 promoter could be enhanced by Sp1 overexpression. MTA2 knockdown impairs invasion and metastasis of gastric cancer cells, and attenuates xenografts growth in vivo. Sp1 regulates MTA2 expression at transcriptional level.
    Full-text · Article · Sep 2013 · Molecular Cancer
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    • "We observe down regulation of corneodesmosin (CDSN), a member of the PSORS1 psoriasis susceptibility locus41, and CD24, a key pro-inflammatory gene, both of which are usually over-expressed in psoriatic skin. The CD24 gene encodes for a mucin-like adhesion molecule, and its over expression has been also repeatedly associated with aggressive tumor progression, metastasis and poor prognosis in various cancers4243. It is also up-regulated in SCC36. "
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    ABSTRACT: Terahertz (THz) radiation lies between the infrared and microwave regions of the electromagnetic spectrum and is non-ionizing. We show that exposure of artificial human skin tissue to intense, picosecond-duration THz pulses affects expression levels of numerous genes associated with non-melanoma skin cancers, psoriasis and atopic dermatitis. Genes affected by intense THz pulses include nearly half of the epidermal differentiation complex (EDC) members. EDC genes, which are mapped to the chromosomal human region 1q21, encode for proteins that partake in epidermal differentiation and are often overexpressed in conditions such as psoriasis and skin cancer. In nearly all the genes differentially expressed by exposure to intense THz pulses, the induced changes in transcription levels are opposite to disease-related changes. The ability of intense THz pulses to cause concerted favorable changes in the expression of multiple genes implicated in inflammatory skin diseases and skin cancers suggests potential therapeutic applications of intense THz pulses.
    Full-text · Article · Aug 2013 · Scientific Reports
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