CD24 is upregulated in inflammatory bowel disease and stimulates cell motility and colony formation

Ahmed, Mohamed A.; Jackson, Darryl; Seth, Rashmi; Robins, Adrian; Lobo, Dileep N.; Tomlinson, Ian; Ilyas, Mohammad

doi:10.1002/ibd.21134

Cited by 34 publications

(36 citation statements)

References 32 publications

(29 reference statements)

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“…We found that the motility of CD24 + cells was higher than that of CD24 -cells. This finding is consistent with a previous study in which forced expression of CD24 in HCT116 human colon cancer cells significantly increased cell migration in wound-healing assays (22). We also performed a wound-healing assay in naïve RMCCA1 cells and found that RMCCA1 cells at the wound edge expressed higher levels of CD24, suggesting that CD24 -cells can give rise to CD24 + cells that have a greater ability to migrate.…”

Section: Discussionsupporting

confidence: 92%

“…We demonstrated for the first time that MMP-7 was highly expressed in CD24 + cholangiocarcinoma cells. Previous studies have demonstrated that MMP-7 plays a key role in the mechanism of cancer invasion via proteolytic cleavage of the extracellular matrix tissues (22). MMP-7 has also been shown to activate other MMPs, such as pro-MMP-2 and pro-MMP-9, and to inhibit E-cadherin function by inducing ectodomain shedding of E-cadherin (23,24).…”

Section: Discussionmentioning

confidence: 99%

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Expression of CD24 in cholangiocarcinoma cells is associated with disease progression and reduced patient survival

Keeratichamroen

Leelawat

Thongtawee³

et al. 2011

Int J Oncol

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Abstract. Cholangiocarcinoma is frequently found to invade local tissues and metastasize to distal organs. We investigated the expression of CD24 in cholangiocarcinoma samples and its prognostic significance. In addition, the cellular function of CD24 was studied in the RMCCA1 cholangiocarcinoma cell line. High CD24 expression significantly correlated with lymph node metastasis and positive surgical margins in cholangiocarcinoma patients. Univariate and multivariate analyses further demonstrated that CD24 expression was significantly associated with the overall survival of these patients (p=0.007 and p=0.040, respectively). For in vitro studies, the magnetic-activated cell sorting (MACS) system was used to isolate CD24 + and CD24 -cell populations from RMCCA1 cells. CD24 + RMCCA1 cells had increased chemoresistance, adhesion (p=0.004), motility (p<0.001), migration (p<0.001) and invasion (p<0.001) capabilities when compared to CD24 -cells. The matrix metalloproteinase (MMP)-7 was significantly elevated in CD24 + RMCCA1 cells (p=0.01). We found that inhibition of CD24 using siRNA silencing significantly decreased the invasive capacity of RMCCA1 cells. Both clinical and in vitro studies suggest that expression of CD24 is associated with cholangiocarcinoma disease progression. CD24 may thus serve as a new target for directed molecular therapy of cholangiocarcinoma. IntroductionCholangiocarcinoma is one of the most aggressive malignant tumors associated with local tissue invasion and a high rate of metastasis and is one of the most common causes of cancer death in Thailand (1). Three-year survival rates of 35-50% are achieved only in a subset of patients who have negative histological margins at the time of surgery (2-5). Palliative therapeutic approaches, including percutaneous and endoscopic biliary drainage, have generally been used for these patients because there is no effective chemotherapeutic treatment for cholangiocarcinoma. Therefore, identification of the molecules involved in cholangiocarcinoma cell progression is crucial for the development of novel drug treatments for this disease.CD24 is a small, heavily glycosylated mucin-like glycosylphosphatidylinositol (GPI)-linked cell surface protein that serves as a ligand for P-selectin, an adhesion receptor on activated endothelial cells and platelets (6). CD24 can be detected in granulocytes, pre-B-cells and keratinocytes (7) and its expression in non-small cell lung cancer, ovarian cancer and hepatocellular carcinoma is associated with poor prognoses (8,9). However, only limited studies have been published on CD24 expression in cholangiocarcinoma (10,11) and there are no data on the mechanism of CD24 involvement in cholangiocarcinoma cell progression. In the present study, we investigated the clinicopathological significance of CD24 expression in human cholangiocarcinoma samples. We also determined the cellular function of CD24 in cholangiocarcinoma cells by isolating CD24 + and CD24 -cells from the RMCCA1 cholangiocarcinoma cell line and assessing cell pro...

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Expression of CD24 in cholangiocarcinoma cells is associated with disease progression and reduced patient survival

Keeratichamroen

Leelawat

Thongtawee³

et al. 2011

Int J Oncol

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“…The antibodies used in this study were validated by Western blotting as described previously [15]. For validation of anti-CD44 antibody (CD44 (156-3C11), cell signalling, #3570) specificity, Western blotting was performed on whole cell lysates of MCF-7 and MDA-MB231 human breast cancer cell lines (obtained from the American Type Culture Collection; Rockville, MD, USA).…”

Section: Validation Of Antibodies' Specificitymentioning

confidence: 99%

A CD44−/CD24+ phenotype is a poor prognostic marker in early invasive breast cancer

Ahmed

Aleskandarany

Rakha

et al. 2011

Breast Cancer Res Treat

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A CD44(-)/CD24(+) phenotype is a poor prognostic marker in early invasive breast cancer. Breast cancer cells with high CD44 and low or absent CD24 (i.e. CD44(+)CD24(-)/low phenotype) are reported to have stem cell features. However, the clinical impact of CD24 and CD44 expression in tumours remains unclear. To explore the immunohistochemical expression of CD44 and CD24 (individually and combined) and their clinical value as prognostic and predictive markers. Immunohistochemical expression of CD24 and CD44 was studied in a large series of early primary invasive breast cancer tumours (n = 1036) prepared as a tissue microarray. Associations between the expression of each marker individually and in combination and clinico-pathological, molecular variables and patients' outcome were investigated. CD24 cytoplasmic expression was significantly associated with poor prognostic variables including high tumour grade, ER-, PR-, HER2(+), p53+ and triple negative (TN) phenotype; P < 0.05. However, CD24 expression was not significantly associated with patients' outcome. Conversely, CD44 expression was associated with favourable prognostic criteria including lower Nottingham prognostic index, ER+, HER2- and luminal phenotype; P < 0.05. Moreover, CD44 expression was found to be an independent predictor of good prognosis. In combination, the CD44(+)/CD24(-) phenotype was associated with the most favourable outcome (84 and 80% 10 year breast cancer survival [BCSS] and metastasis free survival [MFS], respectively). Contrasting this, the CD44(-)/CD24(+) phenotype was associated with the most dismal outcome (62 and 60% 10 years BCSS and MFS, respectively). CD24 and CD44 expression can individually yield prognostic data in breast cancer, but importantly, when both markers are considered; the CD44(+)/CD24(-) phenotype had the best prognosis, while the CD44(-)/CD24(+) phenotype had the worst prognosis. This shows that the relationship between basic cell biology and clinical behaviour is not always straightforward and warrants further investigations of the true clinical impact of breast cancer stem cells.

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“…Likewise, a lack of correlation between CD34 marker and clinical and pathological factors including; lymphatic invasion, gender, age and stage of differentiation were also confirmed in the study by Wang et al (2004). In the study of Ahmed et al (2010), as well as, Nosrati et al (2014) on colorectal cancer, no association was reported between the CD34 expression and clinicopathologic factors. In contrast, increasing the CD34 marker expression was positively correlated with tumor stage, infiltration and lymph node and therefore, it was concluded that this marker in GC is correlated within the disease development (Chen et al, 2008).…”

Section: Discussionmentioning

confidence: 58%

Correlation between CD34 Marker and Clinico-Pathologic Characteristics of Gastric Cancer

Habibi¹,

Ranjbari²,

Rahim³

et al. 2015

International J. of Cancer Research

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One of the most common cancers in the world, especially in underdeveloped countries, is Gastric Cancer (GC) which kills thousands of people annually. It is also prevalent in our country, Iran and according to statistics, it is the most common cancer in men. Since, the relationship between expression of CD34 cell surface markers and many cancers has been approved in the present study, the marker expression association with GC is studied. In this study, a total of 47 paraffin blocks of patients with GC referring to Imam Khomeini hospital in Ahvaz, during 2003-2013 were used. The mean age of 47 patients, including, 35 men (74.5%) and 12 women, was 60±16.05 years old ranging from 24-84. The mean tumor size was 34.5 ranging from 2-12 cm. More than 71% of tumors were intestinal type and the depth of more than 74% of them was in T3 phase. Incidence of marker was positive in only 8 patients (17%) and in rest 39 was negative. The CD34 expression was significantly correlated only with the tumor type (p = 0.00), degree of malignancy (p = 0.00) and neural invasion (p = 0.01). In this study, a positive correlation was observed between the marker expression and three factors of tumor type, degree of differentiation and neural invasion. It was also concluded that due to the negative CD34 expression in 83% of samples, the absence of positive CD34 cells in tumor tissue can be considered as a marker in GC, although it is recommended to do further research with more samples in this context.

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CD24 is upregulated in inflammatory bowel disease and stimulates cell motility and colony formation

Abstract: This is the first study to report upregulation of CD24 in regenerating tissue in IBD. This may be regulated by Wnt signaling and can confer enhanced colony forming ability and enhanced cell motility-features that may be important in tissue healing in the colon.

Cited by 34 publications

References 32 publications

Expression of CD24 in cholangiocarcinoma cells is associated with disease progression and reduced patient survival

Expression of CD24 in cholangiocarcinoma cells is associated with disease progression and reduced patient survival

A CD44−/CD24+ phenotype is a poor prognostic marker in early invasive breast cancer

Correlation between CD34 Marker and Clinico-Pathologic Characteristics of Gastric Cancer

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