CD44 expression and growth factors

Hamada, Junichi; Sawamura, Yuka; Eg, Van Meir

doi:10.2741/a310

Cited by 16 publications

(7 citation statements)

References 38 publications

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“…Upregulation of CD44 and downregulation of CD44 seem to be involved in the EMT process and the acquisition of invasive and metastatic potential (40)(41)(42)(43). In this study, treatment with shRNA-CD44 induced CD44 shedding from the cell surface and significantly decreased cell migration and invasion in SW480 cells.…”

Section: Discussionsupporting

confidence: 48%

CD44 enhances the epithelial-mesenchymal transition in association with colon cancer invasion

et al. 2012

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Abstract. The metastatic process involves the migration and invasion of cancer cells throughout the body to produce secondary tumors at distant sites. Through of epithelial-mesenchymal transition (EMT), cancer cells employ developmental processes to gain migratory and invasive properties. CD44 is the transmembrane adhesion receptor for Hyaluronan (HA) and plays a central role in the remodeling and degradation of HA that leads to cell migration, as well as to cancer invasion and metastasis. CD44 is highly expressed in primary and metastatic colon cancer but lowly expressed in normal tissues. We evaluated the impact of CD44 on EMT and invasion of colon cancer cells. The functional role of CD44 in EMT was determined by the overexpression or knockdown of CD44. CD44 was overexpressed by transfection with plasmid-RT-PCR product and knockdown of CD44 by small hairpin RNA (shRNA)-mediated depletion of CD44 in SW480 colon cancer cells. Morphological changes were evaluated by confocal laser microscopy in the culture media. The expression of EMT markers (E-cadherin/N-cadherin/vimentin/fibronectin/actin/ MMPs) and CD44/EGFR/PI3K-Akt signaling were evaluated using western blotting. The influence of EMT in tumor biology was assessed with proliferation, migration and invasion assays. EMT changes increased in CD44-overexpressing SW480 cells and decreased in CD44 knockdown cells. CD44 activation induced expression of EGFR and activation of phosphatidylinositol 3' kinase (PI3K)/Akt and expression of glycogen synthase kinase-3 β (GSK-3β). In terms of EMT markers, CD44 downregulated E-cadherin expression, upregulated N-cadherin, α-actin, vimentin, fibronectin and MT1-MMP, and inhibited the formation of the membrane-associated E-cadherin-β-catenin complex, which resulted in cell invasion and migration.

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Section: Discussionsupporting

confidence: 48%

CD44 enhances the epithelial-mesenchymal transition in association with colon cancer invasion

et al. 2012

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“…In this study, despite the difference in CD44 expression, treatment with CD44 mAb (clone IM7), which induces CD44 shedding from the cell surface [50], significantly decreased cell migration and invasion in MCF-7-14 and its clone CL6 cells as well as MDA-MB-231 cells. Although CD44 expression seems to be correlated with mesenchymal marker expression as well as with invasiveness, CD44 may be one of the most important adhesion molecules facilitating cell invasion and metastasis [51]. Furthermore, CD44 expression is, directly or indirectly, regulated by the β-catenin/Tcf-4 signaling pathway, especially in the colorectal cancer precursor lesions, suggesting a role for CD44 in intestinal tumorigenesis [52,53].…”

Section: Discussionmentioning

confidence: 99%

Nuclear β-catenin and CD44 upregulation characterize invasive cell populations in non-aggressive MCF-7 breast cancer cells

Uchino¹,

Kojima

Wada

et al. 2010

BMC Cancer

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BackgroundIn breast cancer cells, the metastatic cell state is strongly correlated to epithelial-to-mesenchymal transition (EMT) and the CD44+/CD24- stem cell phenotype. However, the MCF-7 cell line, which has a luminal epithelial-like phenotype and lacks a CD44+/CD24- subpopulation, has rare cell populations with higher Matrigel invasive ability. Thus, what are the potentially important differences between invasive and non-invasive breast cancer cells, and are the differences related to EMT or CD44/CD24 expression?MethodsThroughout the sequential selection process using Matrigel, we obtained MCF-7-14 cells of opposite migratory and invasive capabilities from MCF-7 cells. Comparative analysis of epithelial and mesenchymal marker expression was performed between parental MCF-7, selected MCF-7-14, and aggressive mesenchymal MDA-MB-231 cells. Furthermore, using microarray expression profiles of these cells, we selected differentially expressed genes for their invasive potential, and performed pathway and network analysis to identify a set of interesting genes, which were evaluated by RT-PCR, flow cytometry or function-blocking antibody treatment.ResultsMCF-7-14 cells had enhanced migratory and invasive ability compared with MCF-7 cells. Although MCF-7-14 cells, similar to MCF-7 cells, expressed E-cadherin but neither vimentin nor fibronectin, β-catenin was expressed not only on the cell membrane but also in the nucleus. Furthermore, using gene expression profiles of MCF-7, MCF-7-14 and MDA-MB-231 cells, we demonstrated that MCF-7-14 cells have alterations in signaling pathways regulating cell migration and identified a set of genes (PIK3R1, SOCS2, BMP7, CD44 and CD24). Interestingly, MCF-7-14 and its invasive clone CL6 cells displayed increased CD44 expression and downregulated CD24 expression compared with MCF-7 cells. Anti-CD44 antibody treatment significantly decreased cell migration and invasion in both MCF-7-14 and MCF-7-14 CL6 cells as well as MDA-MB-231 cells.ConclusionsMCF-7-14 cells are a novel model for breast cancer metastasis without requiring constitutive EMT and are categorized as a "metastable phenotype", which can be distinguished from both epithelial and mesenchymal cells. The alterations and characteristics of MCF-7-14 cells, especially nuclear β-catenin and CD44 upregulation, may characterize invasive cell populations in breast cancer.

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“…Furthermore, several studies have provided evidence that hyaluronan exerts signaling effects through interactions with certain cell surface receptors, such as CD44 and RHAMM (5,6). The predominant receptor for hyaluronan is the cell surface adhesion receptor CD44 that is expressed in most cell types transferring signals from the outside of the cell to the inside in response to hyaluronan binding (7)(8)(9). CD44 exists in several isoforms because of alternative splicing of the gene, which can further undergo extensive post-translational modifications by glycosylation and addition of polysaccharide chains.…”

mentioning

confidence: 99%

Inhibition of Platelet-derived Growth Factor-BB-induced Receptor Activation and Fibroblast Migration by Hyaluronan Activation of CD44

Heldin

2006

Journal of Biological Chemistry

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The extracellular matrix molecule hyaluronan was found to suppress platelet-derived growth factor (PDGF) ␤-receptor activation and PDGF-BB-induced migration of primary human dermal fibroblasts. The suppressive effect of hyaluronan was neutralized by a monoclonal antibody that specifically inhibits hyaluronan binding to its receptor CD44. Moreover, co-immunoprecipitation experiments showed that the PDGF ␤-receptor and CD44 can form a complex. Interestingly, the inhibitory effect of hyaluronan on PDGF ␤-receptor activation was not seen in the presence of the tyrosine phosphatase inhibitor pervanadate. Our observations suggest that hyaluronan suppresses PDGF ␤-receptor activation by recruiting a CD44-associated tyrosine phosphatase to the receptor.

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CD44 expression and growth factors

Cited by 16 publications

References 38 publications

CD44 enhances the epithelial-mesenchymal transition in association with colon cancer invasion

CD44 enhances the epithelial-mesenchymal transition in association with colon cancer invasion

Nuclear β-catenin and CD44 upregulation characterize invasive cell populations in non-aggressive MCF-7 breast cancer cells

Inhibition of Platelet-derived Growth Factor-BB-induced Receptor Activation and Fibroblast Migration by Hyaluronan Activation of CD44

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