Characterization of CD24 expression in intraductal papillary mucinous neoplasms and ductal carcinoma of the pancreas

Ikenaga, Naoki; Ohuchida, Kenoki; Mizumoto, Kazuhiro; Yu, Jun; Kayashima, Tadashi; Hayashi, Akifumi; Nakata, Kohei; Tanaka, Masao

doi:10.1016/j.humpath.2010.04.004

Cited by 45 publications

(32 citation statements)

References 33 publications

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“…The positive rate of CD24 was low in low-grade IPMNs, which was 23.1% (3 of 13), but increased in high-grade IPMNs where positive expression of CD24 was observed in 58.3% (7 of 12). CD24 showed a moderate increasing trend according to the grade of dysplasia in IPMNs ( p = 0.072), which was consistent with a previous study [22]. There was a large overlap between ANXA10 and CD24 in high-grade IPMNs (shown in arrows in Fig 3B ).…”

Section: Resultssupporting

confidence: 91%

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Annexin A10 is a candidate marker associated with the progression of pancreatic precursor lesions to adenocarcinoma

Zhu

Pei

et al. 2017

PLoS ONE

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Annexins are a multigene family of calcium and phospholipid-binding proteins that play important roles in calcium signaling, cell motility, differentiation and proliferation. Our previous mass spectrometry-based proteomics study revealed that annexin A10 (ANXA10) was uniquely overexpressed in pancreatic CD24+ adenocarcinoma cells that were dissected from clinical PDAC tissues but was absent in CD24- adjacent normal cells. The correlation between ANXA10 expression and the progression of pancreatic cancer remains unknown. In this study, we performed an immunostaining assay to evaluate ANXA10 expression in 155 primary human tissue specimens, including normal pancreas, chronic pancreatitis (CP), pancreatic adenocarcinoma (PDAC), pancreatic intraepithelial neoplasia (PanIN, the most important precursor of PDAC), and intraductal papillary mucinous neoplasm (IPMN). The immunostaining result showed that ANXA10 was significantly overexpressed in PanINs, IPMNs, and PDACs but negative in normal pancreas and the majority of chronic pancreatitis tissues. Statistical analysis revealed that ANXA10 expression was significantly associated with PDAC and its precursor lesions (p<0.0001). Abundant ANXA10 expression was predominantly present in pancreatic ductal epithelial cells of PanINs, IPMNs, and tumor cells of PDACs. Since PDAC develops through a series of PanINs which in turn arise from pancreatic ducts, the consistent overexpression of ANXA10 in ductal epithelial cells in PanINs and PDACs but negative in normal pancreatic ducts suggests that ANXA10 could serve as a potential marker indicating the presence of PDAC at its earliest precancerous stages. Double immunostaining of ANXA10 and CD24 showed that there was a large overlap between these two markers in PDAC and high-grade neoplasia lesions. The statistical analysis showed that the coexpression of ANXA10 and CD24 was significantly correlated with the progression of pancreatic precursor lesions towards PDACs.

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Section: Resultssupporting

confidence: 91%

“…Various studies have reported that CD24 expression was highly correlated with the progression of pancreatic cancer [20, 22]. Our previous IHC studies showed that CD24 expression was restricted to the membrane of malignant ducts in PDACs [20] and ductal epithelial cells in PanINs [34].…”

Section: Discussionmentioning

confidence: 99%

Annexin A10 is a candidate marker associated with the progression of pancreatic precursor lesions to adenocarcinoma

Zhu

Pei

et al. 2017

PLoS ONE

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“…These findings are consistent with a previous study, which demonstrated that cholangiocarcinomas highly expressing CD24 tended to be associated with higher incidences of metastasis and worse prognoses (10,11). In addition, many studies have shown that CD24 expression correlates with the aggressiveness of other types of cancer, including pancreatic cancer (17) and hepatocellular carcinoma (18). Taken together, our data indicate that CD24 is involved in the progression and malignant behavior of cholangiocarcinoma.…”

Section: Discussionsupporting

confidence: 93%

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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“…12 Patients with PDAC have a doom prognosis when these tumors were previously shown to have a high level of CD24. 13 Taken together, these observations suggest that studies of CD24 + cells in primary PDAC tissues could provide a means to identify markers involved in pancreatic tumorigenesis and progression.…”

Section: Introductionmentioning

confidence: 85%

Target Proteomic Profiling of Frozen Pancreatic CD24+ Adenocarcinoma Tissues by Immuno-Laser Capture Microdissection and Nano-LC–MS/MS

Zhu

Nie

et al. 2013

J. Proteome Res.

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Cellular heterogeneity of solid tumors represents a common problem in mass spectrometry (MS)-based analysis of tissue specimens. Combining immuno-laser capture microdissection (iLCM) and mass spectrometry (MS) provides a means to study proteins that are specific for pure cell subpopulations in complex tissues. CD24, as a cell surface marker for detecting pancreatic cancer stem cells (CSCs), is directly correlated with the development and metastasis of pancreatic cancer. Herein, we describe an in-depth proteomic profiling of frozen pancreatic CD24+ adenocarcinoma cells from early stage tumors using iLCM and LC-MS/MS, and a comparison with CD24− cells dissected from patient-matched adjacent normal tissues. Approximately 40 nL tissue was procured from each specimen and subjected to tandem MS analysis in triplicate. A total of 2665 proteins were identified, with 375 proteins in common that were significantly differentially expressed in CD24+ versus CD24− cells by at least a 2-fold change. The major groups of the differentially overexpressed proteins are involved in promoting tumor cell migration and invasion, immune escape and tumor progression. Three selected candidates relevant to mediating immune escape, CD59, CD70 and CD74, and a tumor promoter, TGFBI, were further validated by immunohistochemistry analysis on tissue microarrays. These proteins showed significantly increased expression in a large group of clinical pancreatic adenocarcinomas but were negative in all normal pancreas samples. The significant coexpression of these proteins with CD24 suggests that they may play important roles in the progression of pancreatic cancer and could serve as promising prognosis markers and novel therapeutic targets for this deadly disease.

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Characterization of CD24 expression in intraductal papillary mucinous neoplasms and ductal carcinoma of the pancreas

Cited by 45 publications

References 33 publications

Annexin A10 is a candidate marker associated with the progression of pancreatic precursor lesions to adenocarcinoma

Annexin A10 is a candidate marker associated with the progression of pancreatic precursor lesions to adenocarcinoma

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

Target Proteomic Profiling of Frozen Pancreatic CD24+ Adenocarcinoma Tissues by Immuno-Laser Capture Microdissection and Nano-LC–MS/MS

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