OBJECTIVETo evaluate the role of E-cadherin (E-cad) and CDH1 gene encoding E-cad in the occurrence of sporadic or hereditary gastric cancer.

METHODSNineteen normal gastric mucosal issue specimens, 19 specimens of hereditary gastric cancer (diagnosed according to ICG-HGC criteria), and 19 specimens of sporadic gastric cancer examined for E-cad expression and CDH1 promoter methylation using immunohistochemistry and methylation-specific PCR (MSP).

RESULTSThe protein expression of E-cad were significantly reduced in both of the cancer tissues (P<0.001) compared with that in the normal gastric mucosal tissues, and showed no significant difference between the two cancers (P=0.84). CDH1 promoter hypermethylation was found in 10 out of the 19 hereditary gastric cancer tissues, a rate significantly higher than that in sporadic gastric cancer tissues (3/19, P<0.01).

CONCLUSIONCDH1 promoter hypermethylation is probably an important factor contributing to reduced E-cad expression in sporadic gastric cancer but not in hereditary gastric cancer.

Cadherins ; genetics ; metabolism ; DNA Methylation ; Humans ; Promoter Regions, Genetic ; Stomach Neoplasms ; genetics ; metabolism

OBJECTIVETo investigate the expressions of homeobox transcription factor-2 (CDX(2)) and E-cadherin and their relations to the clinicopathological characteristics of gastric carcinoma.

METHODSImmunohistochemistry was performed on 83 human gastric carcinoma specimens and 40 normal gastric mucosa specimens for examining the expressions of CDX(2) and E-cadherin, and the relations of their expression with the tumor differentiation, infiltration and metastasis were analyzed.

RESULTSAccording to the LaurAn classification, the positive expression rate of CDX(2) in intestinal type of gastric carcinoma was 56.86%, and 34.38% in the diffuse type, showing significant difference between the two types (P<0.05). The positivity rate of E-cadherin was also significantly different between the two types (66.67% vs 28.13%, P<0.01). In regard to tumor differentiation, the positivity of CDX(2) and E-cadherin expressions was significantly different between moderately to well differentiated tumors and poorly differentiated ones (P<0.01). The tumors infiltrating mucosal and submucosal layers were significantly different from those infiltrating the muscular and serous membrane layer in the positivity of CDX(2) and E-cadherin expressions (P<0.01), which were also different for the presence of lymph node metastasis (P<0.05). Regression analysis did not reveal significant correlations between CDX(2) and E-cadherin expression in gastric carcinoma (P>0.05).

CONCLUSIONThe abnormal expression of CDX(2) and E-cadherin plays an important role in the development of gastric carcinoma, especially the intestinal type. CDX(2) and E-cadherin may serve as useful markers to predict the prognosis of patients with gastric carcinoma.

Adult ; Aged ; Biomarkers, Tumor ; genetics ; metabolism ; CDX2 Transcription Factor ; Cadherins ; genetics ; metabolism ; Female ; Homeodomain Proteins ; genetics ; metabolism ; Humans ; Male ; Middle Aged ; Stomach Neoplasms ; genetics ; metabolism ; pathology

OBJECTIVE: Xiaotan Sanjie recipe (XTSJ), a Chinese herbal compound medicine, exerts a significant inhibitory effect on gastric cancer (GC) metastasis. This work investigated the mechanism underlying the XTSJ-mediated inhibition of GC metastasis. METHODS: The effect of XTSJ on GC metastasis and the associated mechanism were investigated in vitro, using GC cell lines, and in vivo, using a GC mouse model, by focusing on the expression of Glc-N-Ac-transferase V (GnT-V; encoded by MGAT5). RESULTS: The migration and invasion ability of GC cells decreased significantly after XTSJ administration, which confirmed the efficacy of XTSJ in treating GC in vitro. XTSJ increased the accumulation of E-cadherin at junctions between GC cells, which was reversed by MGAT5 overexpression. XTSJ administration and MGAT5 knockdown alleviated the structural abnormality of the cell-cell junctions, while MGAT5 overexpression had the opposite effect. MGAT5 knockdown and XTSJ treatment also significantly increased the accumulation of proteins associated with the E-cadherin-mediated adherens junction complex. Furthermore, the expression of MGAT5 was significantly lower in the lungs of BGC-823-MGAT5 + XTSJ mice than in those of BGC-823-MGAT5 + solvent mice, indicating that the ability of gastric tumors to metastasize to the lung was decreased in vivo following XTSJ treatment. CONCLUSION XTSJ prevented GC metastasis by inhibiting the GnT-V-mediated E-cadherin glycosylation and promoting the E-cadherin accumulation at cell-cell junctions. Please cite this article as: Huang N, He HW, He YY, Gu W, Xu MJ, Liu L. Xiaotan Sanjie recipe, a compound Chinese herbal medicine, inhibits gastric cancer metastasis by regulating GnT-V-mediated E-cadherin glycosylation. J Integr Med. 2023; 21(6): 561-574.
Male ; Mice ; Animals ; Stomach Neoplasms/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Glycosylation ; Cell Line, Tumor ; Cadherins/metabolism*

OBJECTIVETo explore the hematopoietic pathophysiology of myelodysplastic syndrome (MDS) at stem/progenitor cell level by analyzing the gene expression profiles associated with hematopoiesis.

METHODSThe differentially expressed genes which were involved in the hematopoiesis were screened by microarray using CD34(+) cells from MDS patients firstly. RQ-PCR was then applied to validate the screened genes using CD34(+) cells from MDS-RA patients who had normal karyotype. The linkages with hematopoiesis among these validated genes were analyzed.

RESULTSAmong the differentially expressed genes in CD34(+) cells of MDS-RA patients, Rap1GAP was up-regulated significantly (P < 0.01). Cadherins, which can interplay with Rap1, including N-cadherin and E-cadherin, were down-regulated significantly (P < 0.01). β-catenin, a downstream effector of cadherins, was highly expressed in MDS-RA patients (P < 0.01). c-myc binding protein was down-regulated (P < 0.01), and c-myc promoter binding protein was up-regulated (P < 0.01). Rac1, Rac2 and Cdc42, which belong to RhoGTPases family and are associated with the cell morphology and hematopoiesis, were all expressed highly in MDS-RA patients (P < 0.01).

CONCLUSIONThe abnormal expression of cadherin, β-catenin and c-myc associated genes were closely related to the dysplastic hematopoiesis of MDS. The down regulation of cadherin was associated with the positive feedback mechanism between Rap1 and cadherin. The aberrant expression of Rac1, Rac2 and Cdc42 may contribute to the morphological dysplasia of MDS.

Cadherins ; genetics ; metabolism ; Gene Expression ; Gene Expression Profiling ; Genes, myc ; Humans ; Myelodysplastic Syndromes ; genetics ; metabolism ; beta Catenin ; genetics ; rap1 GTP-Binding Proteins ; genetics ; metabolism

Animals ; Cadherins ; metabolism ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Catenins ; metabolism ; Epithelial-Mesenchymal Transition ; drug effects ; genetics ; Humans ; Liver Neoplasms ; metabolism ; pathology ; MicroRNAs ; genetics ; metabolism ; Transforming Growth Factor beta ; pharmacology

OBJECTIVETo investigate the relationship between methylation of the CDH1 gene promoter on the expression of E-cadherin and β-catenin, and to evaluate the correlation with clinicopathological characteristics of the colonic carcinoma.

METHODSMethylation specific PCR (MSP) was used to detect CDH1 gene promoter methylation in the cancer tissue, adjacent tissues and normal tissues in 68 patients. The expression of E-cadherin and β-catenin was determined by immunohistochemistry staining.

RESULTSThe positive rate of CDH1 gene promoter methylation was 32.4% in adjacent tissues and 57.4% in cancer tissue, while no detectable methylation was found in all the normal tissues. The difference was statistically significant. The positive rate of E-cadherin was 92.6% in the normal tissues, 66.2% in the adjacent tissues and 44.1% in the cancer tissues. In all normal tissues, β-catenin was expressed only at the cellular membrane but not in the cytosol or nucleus, while the expression of β-catenin was present in the cytosol or nucleus in 29.4% of the adjacent tissues and 50.0% of the cancer tissues. The positive rate of CDH1 gene promoter methylation was negatively correlated with E-cadherin expression(r=-0.312, P=0.01) and positively correlated with β-catenin cytosolic/nucleus expression(r=0.309, P=0.018). The differentiation and metastasis of colonic carcinoma were associated with the aberrant expression of E-cadherin, β-catenin, and methylation of CDH1 promoter (P<0.05).

CONCLUSIONCDH1 gene promoter methylation may lead to aberrant expression of E-cadherin and β-catenin in colonic carcinoma, and may play an important role in promoting the invasion of tumor.

Adult ; Aged ; Aged, 80 and over ; Cadherins ; genetics ; metabolism ; Colonic Neoplasms ; genetics ; metabolism ; DNA Methylation ; Female ; Humans ; Male ; Middle Aged ; Promoter Regions, Genetic ; beta Catenin ; genetics ; metabolism

OBJECTIVETo investigate the expression of ALDH1, CXCR4 and E-cadherin in gastric carcinoma and their roles in lymphatic metastasis.

METHODSSurgical specimens from 127 cases of gastric carcinoma were examined for expressions of ALDH1, CXCR4 and E-cadherin immuohistochemistry with 60 adjacent tissues as control. The associations of ALDH1, CXCR4 and E-cadherin with the clinicopathological pfeatures, 5-year survival rate and lymph node metastasis of the patients were analyzed.

RESULTSALDH1, CXCR4 and E-cadherin were positive in 57.5% (73/127), 63.8% (81/127), and 36.2% (46/127) of the gastric carcinoma tissues, respectively, showing significant differences from the rates in the adjacent tissues (P<0.05). The expression of ALDH1 was significantly correlated with TNM stage and lymph node metastasis (P<0.05), CXCR4 was significantly correlated with the invasion depth, differentiation, TNM stage and lymph node metastasis of the tumor (P<0.05), and E-cadherin was significantly correlated with the invasion depth, differentiation and lymph node metastasis (P<0.05). The positivity rates of ALDH1, CXCR4 and E-cadherin were higher in cases with lymph node metastasis than in those without metastasis. E-cadherin expression was inversely correlated with ALDH1 and CXCR4 expression, and the latter two were positively correlated (P<0.001). Overexpressions of ALDH1 and CXCR4 and a decreased expression of E-cadherin were all related to a poor prognosis of the patients (P<0.05). The expressions ofALDH1, CXCR4 and E-cadherin were all independent prognostic factors of gastric carcinoma.

CONCLUSIONThe expressions of ALDH1, CXCR4 and E-cadherin are associated with the invasion, metastasis and prognosis of gastric carcinoma, and their combined detection provides important evidence for predicting the progression and prognosis of gastric carcinoma.

Cadherins ; genetics ; metabolism ; Carcinoma ; genetics ; metabolism ; Disease Progression ; Humans ; Isoenzymes ; genetics ; metabolism ; Lymphatic Metastasis ; Prognosis ; Receptors, CXCR4 ; genetics ; metabolism ; Retinal Dehydrogenase ; genetics ; metabolism ; Stomach Neoplasms ; genetics ; metabolism ; Survival Rate

OBJECTIVETo evaluate the role of E-cadherin (E-cad) and CDH1 gene encoding E-cad in the occurrence of sporadic or hereditary gastric cancer.

METHODSNineteen normal gastric mucosal issue specimens, 19 specimens of hereditary gastric cancer (diagnosed according to ICG-HGC criteria), and 19 specimens of sporadic gastric cancer examined for E-cad expression and CDH1 promoter methylation using immunohistochemistry and methylation-specific PCR (MSP).

RESULTSThe protein expression of E-cad were significantly reduced in both of the cancer tissues (P<0.001) compared with that in the normal gastric mucosal tissues, and showed no significant difference between the two cancers (P=0.84). CDH1 promoter hypermethylation was found in 10 out of the 19 hereditary gastric cancer tissues, a rate significantly higher than that in sporadic gastric cancer tissues (3/19, P<0.01).

CONCLUSIONCDH1 promoter hypermethylation is probably an important factor contributing to reduced E-cad expression in sporadic gastric cancer but not in hereditary gastric cancer.

Adult ; Cadherins ; metabolism ; DNA Methylation ; Female ; Humans ; Male ; Middle Aged ; Promoter Regions, Genetic ; Stomach Neoplasms ; genetics ; metabolism ; pathology

OBJECTIVETo detect the expression of the protein of TGF-beta1 and E-cadherin in the primary and metastatic lesions of ovarian carcinoma and explore the mechanism of the metastasis of ovarian carcinoma.

METHODSImmunohistochemistry (IHC) was performed to detect the expression of TGF-beta1 and E-cadherin proteins in primary and metastatic ovarian carcinoma, benign epithelial ovarian tumor and normal ovarian tissue.

RESULTSThe expression of TGF-beta1 was significantly higher in ovarian carcinoma (67.2%) than in benign tumors (28.6%) and normal ovarian tissue (18.9%) (Chi2=26.94, P<0.001), but E-cadherin expression showed a reverse pattern. TGF-beta1 expression in the primary ovarian carcinoma carcinoma was associated with the FIGO stage, lymph metastasis and ascites of the tumor (P=0.01, P=0.01, and P=0.04, respectively). E-cadherin expression in the tumor was associated with the differentiation (P=0.02) and lymph metastasis of ovarian carcinoma (P=0.04). The expressions of TGF-beta1 and E-cadherin were all significantly lower in the primary tumors than in the metastatic tumor (Chi2=4.70, P=0.03; Chi2=5.91, P=0.015). A significant correlation was found between the expressions of the TGF-beta1 and E-cadherin in the primary carcinoma (Kappa value of -0.32, P=0.01).

CONCLUSIONTGF-beta1 and E-cadherin are closely associated with the metastasis of ovarian carcinoma and might be potential targets for controlling the metastasis of ovarian carcinoma.

Adult ; Cadherins ; genetics ; metabolism ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; Neoplasm Metastasis ; Ovarian Neoplasms ; metabolism ; pathology ; Peritoneal Neoplasms ; metabolism ; secondary ; Transforming Growth Factor beta1 ; genetics ; metabolism

E-cadherin is a cell adhesion molecule that plays an important role in maintaining renal epithelial polarity and integrity. The purpose of this study was to determine the exact cellular localization of E-cadherin in pig kidney. Kidney tissues from pigs were processed for light and electron microscopy immunocytochemistry, and immunoblot analysis. E-cadhedrin bands of the same size were detected by immunoblot of samples from rat and pig kidneys. In pig kidney, strong E-cadherin expression was observed in the basolateral plasma membrane of the tubular epithelial cells. E-cadherin immunolabeling was not detected in glomeruli or blood vessels of pig kidney. Double-labeling results demonstrated that E-cadherin was expressed in the calbindin D28k-positive distal convoluted tubule and H(+)-ATPase-positive collecting duct, but not in the aquaporin 1-positive, N-cadherin-positive proximal tubule. In contrast to rat, E-cadherin immunoreactivity was not expressed at detectable levels in the Tamm-Horsfall protein-positive thick ascending limb of pig kidney. Immunoelectron microscopy confirmed that E-cadherin was localized in both the lateral membranes and basal infoldings of the collecting duct. These results suggest that E-cadherin may be a critical adhesion molecule in the distal convoluted tubule and collecting duct cells of pig kidney.
Animals ; Blotting, Western/veterinary ; Cadherins/*genetics/metabolism ; Cell Membrane/*metabolism/ultrastructure ; *Gene Expression Regulation ; Kidney/*metabolism ; Male ; Microscopy, Electron, Transmission/veterinary ; Sus scrofa/*genetics/metabolism