Overexpression of LI-cadherin in gastric cancer is associated with lymph node metastasis

Ko, Samuel

doi:10.1016/s0006-291x(04)00996-9

Cited by 15 publications

(22 citation statements)

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“…The expression of CDH17 protein was detected in 67% of gastric carcinomas that were correlated with depth of tumor invasion, tumor stage and amount of stromal tissue. It was recently reported that CDH17 mRNA expression is an independent factor associated with lymph node metastasis [8,9]. Furthermore, our study demonstrated an association between CDH17 expression and poor prognosis.…”

Section: Discussionsupporting

confidence: 77%

“…Quantitative RT-PCR analysis had confirmed that over 70% of gastric carcinoma overexpressed CDH17 and the expression levels was significantly associated with depth of tumor invasion [20]. Recent reports indicated that the expression of CDH17 was correlated with lymph node metastasis [8,9]. Therefore, CDH17 could be a novel prognostic factor of gastric carcinoma.…”

Section: Introductionmentioning

confidence: 94%

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Clinicopathological significant and prognostic influence of cadherin-17 expression in gastric cancer

et al. 2005

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Cadherin-17 (CDH17), also called liver-intestine cadherin, is a structurally unique member of the cadherin superfamily. Our serial analysis of gene expression demonstrated that CDH17 was one of the most up-regulated genes in advanced gastric carcinomas. CDH17 expression is known to be regulated by Cdx2. In the present study, we examined the expression of CDH17 in primary gastric carcinoma tissues by immunohistochemistry, and analyzed the correlation of CDH17 expression with clinicopathological characteristics and patients prognosis. CDH17 expression was detected in 63/94 (67%) of gastric adenocarcinomas in addition to intestinal metaplasia. The expression of CDH17 tended to be associated with intestinal type carcinoma, and carcinomas with CDH17 expression was significantly more frequent in advanced stage cases (80%) than in early stage (53%). The prognosis of patients with positive CDH17 expression was significantly poorer than that of the negative cases (P=0.0314). However, multivariate analysis revealed that CDH17 was not an independent prognostic factor. Six of seven cases that showed positive expression of Cdx2 simultaneously expressed CDH17 protein. These results suggested that the expression of CDH17 was characteristic of the advanced gastric carcinoma that is associated with poor prognosis.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 94%

Clinicopathological significant and prognostic influence of cadherin-17 expression in gastric cancer

et al. 2005

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“…Among the various growth-and metastasis-associated genes up-regulated in MUC4-overexpressing cells are LI-cadherin, CEACAM6, tumor-associated calcium signal transducer-2, AnnexinA1, thrombomodulin, epiregulin, S100A4, and macrophage inhibitory cytokine 1 (34-36). An up-regulation of LI-cadherin has been shown to correlate with lymph node metastasis in gastric cancer (37,38). Lymph node is one of the most metastasized sites in pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

MUC4 Mucin Potentiates Pancreatic Tumor Cell Proliferation, Survival, and Invasive Properties and Interferes with Its Interaction to Extracellular Matrix Proteins

Chaturvedi¹,

Singh²,

Moniaux³

et al. 2007

Molecular Cancer Research

154

201

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MUC4, a transmembrane mucin, is aberrantly expressed in pancreatic adenocarcinomas while remaining undetectable in the normal pancreas. Recent studies have shown that the expression of MUC4 is associated with the progression of pancreatic cancer and is inversely correlated with the prognosis of pancreatic cancer patients. In the present study, we have examined the phenotypic and molecular consequences of MUC4 silencing with an aim of establishing the mechanistic basis for its observed role in the pathogenesis of pancreatic cancer. The silencing of MUC4 expression was achieved by stable expression of a MUC4-specific short hairpin RNA in CD18/HPAF, a highly metastatic pancreatic adenocarcinoma cell line. A significant decrease in MUC4 expression was detected in MUC4-knockdown (CD18/HPAF-siMUC4) cells compared with the parental and scrambled short interfering RNA -transfected (CD18/HPAF-Scr) control cells by immunoblot analysis and immunofluorescence confocal microscopy. Consistent with our previous observation, inhibition of MUC4 expression restrained the pancreatic tumor cell growth and metastasis as shown in an orthotopic mouse model. Our in vitro studies revealed that MUC4-associated increase in tumor cell growth resulted from both the enhanced proliferation and reduced cell death. Furthermore, MUC4 expression was also associated with significantly increased invasiveness (P V 0.05) and changes in actin organization. The presence of MUC4 on the cell surface was shown to interfere with the tumor cell-extracellular matrix interactions, in part, by inhibiting the integrin-mediated cell adhesion. An altered expression of growth-and metastasis-associated genes (LI-cadherin, CEACAM6, RAC1, AnnexinA1, thrombomodulin, epiregulin, S100A4, TP53, TP53BP, caspase-2, caspase-3, caspase-7, plakoglobin, and neuregulin-2) was also observed as a consequence of the silencing of MUC4. In conclusion, our study provides experimental evidence that supports the functional significance of MUC4 in pancreatic cancer progression and indicates a novel role for MUC4 in cancer cell signaling. (Mol Cancer Res 2007;5(4):309 -20)

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“…In mice and humans, LI cadherin is expressed only in the epithelial cells of the small and large intestine [12,13] . LI cadherin expression has been investigated in various malignant tumors, such as gastric [14][15][16] , hepatocellular [17] , colorectal [18] , pancreatic [19] and intrahepatic cholangiocellular [20] carcinoma. In gastric and hepatocellular carcinoma, LI cadherin is overexpressed and associated with lymph node metastasis and poor prognosis [14,15,17] , but lower expression of LI cadherin is associated with lymph node metastasis, dedifferentiation and poor prognosis in colorectal, pancreatic and intrahepatic cholangiocellular carcinoma [18][19][20] .…”

Section: Introductionmentioning

confidence: 99%

Liver-Intestine Cadherin Expression Is Associated with Intestinal Differentiation and Carcinogenesis in Intraductal Papillary Mucinous Neoplasm

Morimatsu¹,

Aishima²,

Kayashima³

et al. 2012

Pathobiology

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Objectives: Intraductal papillary mucinous neoplasms (IPMN) are classified into four phenotypes according to the WHO classification. Recently, intestinal-type IPMN has been suggested to grow with a distinct carcinogenetic pathway. Like mucin 2, oligomeric mucus/gel forming (MUC2) and caudal-related homeobox 2 (CDX2), liver-intestine cadherin (LI cadherin) is an intestine-specific marker. We aimed to investigate the roles of LI cadherin expression in IPMN. Methods: We examined LI cadherin expression in 135 cases of IPMN by immunohistochemical staining and the quantitative real-time reverse-transcription polymerase chain reaction. Results: LI cadherin protein and mRNA levels were significantly higher in intestinal-type IPMN than in nonintestinal-type IPMN (protein level, p < 0.001; mRNA level, p = 0.0312). A positive correlation was found between protein and mRNA of LI cadherin (p = 0.0037). The positivity rates of LI cadherin expression were significantly higher in CDX2-positive cases than in CDX2-negative cases (p < 0.001). In 41 intestinal-type IPMNs, LI cadherin-positive rates tended to increase gradually, from IPMN with low-grade dysplasia (IPMN-L) to IPMN with an associated invasive carcinoma (IPMN-IC) [IPMN-L vs. IPMN with high-grade dysplasia (IPMN-H); p = 0.0357, IPMN-L vs. IPMN-IC; p = 0.0230] and positively correlated with the Ki-67 labeling index (p = 0.0408), whereas this tendency was not recognized in nonintestinal-type IPMNs. Conclusions: LI cadherin is associated with an intestinal phenotype and an ‘intestinal pathway’ of carcinogenesis in IPMN.

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Overexpression of LI-cadherin in gastric cancer is associated with lymph node metastasis

Cited by 15 publications

References 0 publications

Clinicopathological significant and prognostic influence of cadherin-17 expression in gastric cancer

Clinicopathological significant and prognostic influence of cadherin-17 expression in gastric cancer

MUC4 Mucin Potentiates Pancreatic Tumor Cell Proliferation, Survival, and Invasive Properties and Interferes with Its Interaction to Extracellular Matrix Proteins

Liver-Intestine Cadherin Expression Is Associated with Intestinal Differentiation and Carcinogenesis in Intraductal Papillary Mucinous Neoplasm

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