OBJECTIVETo investigate the intracellular localization of S100A4 in gastric carcinoma cells and the relationship between S100A4 expression status and lymph node metastasis of gastric carcinoma.

METHODSWestern blotting analysis was performed to locate the expression of S100A4 protein in sub-fraction components of frozen tissues. S100A4 protein expression was also determined by immunohistochemical method in 131 samples of gastric cancer and 20 samples of matched metastatic lymph nodes.

RESULTSThirty-two of 131 (24.4%) gastric carcinoma showed positive S100A4 nuclear expression and 50/131 (38.2%) carcinoma showed positive cytoplasmic expression. In 32 samples with positive S100A4 nuclear expression, 30 (93.8%) carcinomas had positive lymph node metastases. S100A4 nuclear expression level was higher in gastric carcinoma with lymph node metastasis (29.1%) than that without lymph node metastasis (7.1%) (P=0.016).

CONCLUSIONNuclear expression of S100A4 is associated with lymph node metastasis of gastric carcinoma.

Cell Nucleus ; metabolism ; Humans ; Lymphatic Metastasis ; Neoplasm Staging ; S100 Calcium-Binding Protein A4 ; S100 Proteins ; metabolism ; Stomach Neoplasms ; metabolism ; pathology

OBJECTIVETo investigate the expression levels of nm23, P53, and S100A4 in gastric carcinoma and their relationships with clinicopathologic parameters and metastasis potential.

METHODSPathological specimens from gastric carcinoma,matched para-tumor tissues, metastatic lymph node and distant metastatic tissues were examined for the expression levels of nm23, P53, and S100A4 proteins by tissue microarray technique and immunohistochemistry.

RESULTSThe expression levels of P53 and S100A4 were upregulated (P< 0.01), while the expression of nm23 downregulated (P< 0.05) in gastric carcinoma compared with non-tumor tissues. S100A4 expression was significantly higher in distant metastatic tissues, while nm23 lower in metastatic lymph nodes than those in cancer tissues. Upregulating expression levels of nm23, P53, and S100A4 were significantly correlated with some malignant behaviour of gastric cancer. The expression rates of nm23+/P53+, P53+/S100A4+, and nm23+/S100A4+ immunohistochemical phenotypes were 48/74 (64.9%), 50/74 (67.6%), and 39/74 (52.7%). P53+/S100A4+, nm23+/S100A4+, and nm23+/P53+/S100A4+ phenotypes were associated with high metastasis potential of gastric cancer.

CONCLUSIONSAlteration of nm23, P53, and S100A4 expression may contribute to the development of gastric carcinoma. Nm23 and S100A4 proteins play a critical role in tumor metastasis. Co-detection of the expression of P53, nm23, and/or S100A4 can be used to evaluate high metastasis potential of gastric cancer.

Female ; Gene Expression ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Male ; Middle Aged ; NM23 Nucleoside Diphosphate Kinases ; metabolism ; Neoplasm Invasiveness ; Neoplasm Staging ; S100 Calcium-Binding Protein A4 ; S100 Proteins ; metabolism ; Stomach Neoplasms ; metabolism ; pathology ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVEThe purpose of the present study was to explore the relationship between the expression of S100A4 and E-cad protein and some clinicopathological factors such as histological types, TNM stages, lymph node metastasis and prognosis in non-small cell lung cancer (NSCLC), and analyze whether there is a correlation between them.

METHODSThe expression of S100A4 protein and E-cad protein was detected with immunohistochemical SP technique in 116 non-small-cell lung cancers.

RESULTSThe positive immunohistochemical staining for S100A4 protein was observed in 64 out of the 116 patients, with a positive rate of 55.2%. The expression rate of S100A4 protein was associated with age, tumor size, lymph node metastasis and prognosis of NSCLC. The expression of S100A4 protein was not significantly related with histological types, sex and TNM stages. The positive rate of E-cad protein expression was 65.5%. The expression of E-cad protein was associated with TNM staging, lymph node metastasis and prognosis of NSCLC. The expression of E-cad protein had no significant correlation with histological types, patient age and sex. An inverse correlation between the levels of S100A4 and E-cad protein expression was found (P < 0.005).

CONCLUSIONExpression of S100A4 protein and loss of E-cad protein expression are significantly associated with tumor progression, and may become valuable markers in prediction of biological behavior and tendency of metastasis of non-small-cell lung cancers.

Biomarkers, Tumor ; Cadherins ; metabolism ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; S100 Calcium-Binding Protein A4 ; S100 Proteins ; metabolism ; Survival Rate

OBJECTIVETo study the role of S100A4 in the carcinogenesis, development, invasion and metastasis of esophageal squamous cell carcinoma.

METHODSImmunohistochemistry was used to detect the expressions of S100A4, MMP-2 and E-cadherin proteins in 100 cases of surgically resected esophageal squamous cell carcinoma specimens. RT-PCR and Western blot were used to detect the expressions of S100A4 mRNA and protein in esophageal squamous cell carcinoma line EC-1 and TE-1. Boyden-chamber model in vitro was utilized to detect the invasion ability of EC-1 and TE-1 cells.

RESULTSThe positivity rate of S100A4 protein was 52.0% was in esophageal carcinoma tissues, significantly higher than that in normal tissues (26.0%) (P<0.01). The expression of S100A4 was related to tumor grading, invasive depth and lymph node metastasis (P<0.05). In esophageal carcinoma, the expression of S100A4 was positively correlated to MMP-2 expression (P<0.01), but inversely to E-cadherin expression (P<0.05). The expressions of S100A4 mRNA (0.894-/+0.021) and protein (0.897-/+0.053) in EC-1 cells were significantly higher than those in TE-1 (0.812-/+0.040 and 0.645-/+0.089, respectively, P<0.01), and the invasion ability of EC-1 cells was significantly higher than that of TE-1 cells (91.00-/+17.44 vs 61.80-/+11.10, P<0.01).

CONCLUSIONThe overexpression of S100A4 in esophageal squamous cell carcinoma tissue and highly invasive EC-1 cells may contribute to the carcinogenesis, development, invasion and metastasis of esophageal squamous cell carcinoma.

Adult ; Aged ; Cadherins ; metabolism ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Line, Tumor ; Esophageal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Male ; Matrix Metalloproteinase 2 ; metabolism ; Middle Aged ; S100 Calcium-Binding Protein A4 ; S100 Proteins ; metabolism

OBJECTIVETo observe the expressions of metastasis-associated protein (S100A4) and matrix metalloproteinase 9 (MMP9) in human non-small cell lung cancer (NSCLC) and investigate their correlations to the infiltration, metastasis and prognosis of NSCLC.

METHODSThe expressions of S100A4 and MMP9 were detected in 41 NSCLC specimens and 6 normal lung tissue specimens using immunohistochemistry with SP method. Univariate and multivariate survival analysis were used to analyze the correlations of S100A4 and MMP9 to the clinicopathological characteristics and progrnosis of NSCLC.

RESULTSCompared with normal lung tissues, NSCLC showed significantly increased positivity for S100A4 and MMP9 expression (P<0.05); their expression were significantly higher in adenocarcinoma than in squamous cell carcinoma (P<0.01), and higher in metastatic NSCLC than in that without lymphatic metastasis (P<0.01). The positive expression rates of S100A4 and MMP9 were significantly higher in tumors in TNM stages III +IV than in stages II+I (P<0.05). S100A4 expression was positively correlated to tumor size (P<0.001), while MMP9 was inversely correlated to tumor differentiation (P<0.05). The expressions of S100A4 and MMP9 were both correlated to lymphatic metastasis, TNM stages and pathological types (P<0.05), and they also showed a mutual correlation (P<0.01). Univariate survival analysis confirmed the effects of histological types, lymphatic metastasis, clinical TNM stages and expressions of S100A4 and MMP9 on the survival time of NSCLC patients (P<0.001). Multivariate survival analysis identified clinical TNM stages and expressions of S100A4 and MMP9 as the independent factors affecting the prognosis of NSCLC (P<0.05).

CONCLUSIONThe expressions of S100A4 and MMP9 are up-regulated in NSCLC and have significant correlations to the clinical and biological behaviors of NSCLC. S100A4 and MMP9 status are independent prognostic predictors of NSCLC, and detection of their expressions may help evaluate the prognosis of NSCLC.

Adult ; Aged ; Carcinoma, Non-Small-Cell Lung ; metabolism ; pathology ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Lung Neoplasms ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Matrix Metalloproteinase 9 ; biosynthesis ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; S100 Calcium-Binding Protein A4 ; S100 Proteins ; biosynthesis

OBJECTIVEPancreatic cancer is one of the most deadly cancers, which is characterized by its high metastatic potential. S100A4 is a major prometastatic protein involved in tumor invasion and metastasis which precise role in pancreatic cancer has not been fully investigated. We knocked down the S100A4 gene in the Bxpc-3 pancreatic cancer cell line via RNA interference to study the changes in cell behavior.

METHODSReal-time polymerase chain reaction and western blotting were used to detect mRNA and protein expression levels of S100A4, matrix metalloproteinase (MMP)-2, E-cadherin and thrombospondin (TSP)-1. Transwell chambers were used to detect the migration and invasion abilities; a cell adhesion assay was used to detect adhesion ability; colony forming efficiency was used to detect cell proliferation; flow cytometry was used to detect apoptosis.

RESULTSS100A4 mRNA expression was reduced to 17% after transfection with S100A4-siRNA, and protein expression had a similar trend. mRNA and protein expression of MMP-2 was reduced and that of E-cadherin and TSP-1 was elevated, indicating that S100A4 affects their expression. S100A4-silenced cells exhibited a marked decrease in migration and invasiveness and increased adhesion, whereas overall proliferation and apoptosis were not overtly altered.

CONCLUSIONS100A4 and its downstream factors play important roles in pancreatic cancer invasion, and silencing A100A4 can significantly contain the invasiveness of pancreatic cancer.

Apoptosis ; genetics ; physiology ; Blotting, Western ; Cadherins ; genetics ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Matrix Metalloproteinase 2 ; genetics ; metabolism ; Pancreatic Neoplasms ; genetics ; metabolism ; RNA Interference ; RNA, Small Interfering ; Real-Time Polymerase Chain Reaction ; S100 Calcium-Binding Protein A4 ; S100 Proteins ; genetics ; metabolism ; Thrombospondin 1 ; genetics ; metabolism

OBJECTIVETo explore the role of S100A4 in the epithelial-mesenchymal transition (EMT) in esophageal squamous cell carcinoma and its possible molecular mechanism.

METHODSThree chemically synthesized S100A4 siRNA sequences were transiently transfected into esophageal carcinoma EC9706 cells. EC9706 cells transfected with negative siRNA, lipofectamine 2000, and vacant EC9706 cells were used as control. Fluorescence quantitative RT-PCR and Western blot were used to detect the inhibition rate of S100A4 siRNA. S100A4 siRNA2 with the best inhibition rate was chosen to transiently transfect into EC9706 cells under the same conditions. The EC9706 cells transfected with negative siRNA, lipofectamine 2000 and vacant EC9706 cells were also used as control. Fluorescence quantitative RT-PCR and Western blot were used to detect the mRNA and protein expressions of E-cadherin, vimentin and snail. The morphology of EC9706 cells was observed under an inverted microscope. Boyden chamber and scratch test were used to detect the invasion and migration ability of EC9706 cells, and CCK8 assay was used to detect the proliferation ability of EC9706 cells. EC9706 cells transfected with S100A4 siRNA2 were further transfected with snail eukaryotic expression vector. The EC9706 cells transfected with S100A4 siRNA, EC9706 cells transfected with snail eukaryotic expression vector and vacant EC9706 cells were used as control. The above indexes of all the groups were observed, too.

RESULTSThe S100A4 mRNA and protein expression levels of the S100A4 siRNA2 group were 0.417 ± 0.041 and 0.337 ± 0.039, the transmembrane cell number was 61.608 ± 8.937, the scratch healing distance was (0.216 ± 0.064) mm, the A value was 0.623 ± 0.084, the E-cadherin mRNA and protein levels were 0.619 ± 0.032 and 0.495 ± 0.034, the vimentin mRNA and protein levels were 0.514 ± 0.032 and 0.427 ± 0.028, the snail mRNA and protein levels were 0.573 ± 0.029 and 0.429 ± 0.041. These data were significantly different with the liposome group, the negative control group and the blank group (P < 0.05 for all). After the S100A4 siRNA2 treatment for 24 h, the appearance of EC9706 cells changed to epithelial cell morphology. The transmembrane cell number and the scratch healing distance of the S100A4 siRNA2+snail eukaryotic expression vector group were (69.382 ± 9.666) cells and (0.274 ± 0.029) mm, the A value was 0.823 ± 0.101, the snail mRNA and protein levels were 0.704 ± 0.037 and 0.625 ± 0.031, the vimentin mRNA and protein levels were 0.712 ± 0.046 and 0.609 ± 0.038, and these data were significantly higher than those of the Sl00A4 siRNA2 group (P < 0.05 for all). The E-cadherin mRNA and protein levels of the S100A4 siRNA2+eukaryotic expression vector group were 0.437 ± 0.038 and 0.381 ± 0.031, significantly lower than those of the S100A4 siRNA2 group (P < 0.05 for all). However, snail had no effect on the morphology of EC9706 cells.

CONCLUSIONSS100A4 may be involved in the EMT process of esophageal squamous-cell carcinoma by regulating the expression of snail and then plays a role in the invasion and metastasis of esophageal carcinoma.

Cadherins ; analysis ; Carcinoma, Squamous Cell ; metabolism ; pathology ; physiopathology ; Cell Line, Tumor ; Epithelial Cells ; Epithelial-Mesenchymal Transition ; Esophageal Neoplasms ; metabolism ; pathology ; physiopathology ; Humans ; Indicators and Reagents ; Lipids ; RNA, Messenger ; analysis ; RNA, Small Interfering ; analysis ; physiology ; S100 Calcium-Binding Protein A4 ; S100 Proteins ; antagonists & inhibitors ; genetics ; physiology ; Snail Family Transcription Factors ; Transcription Factors ; analysis ; genetics ; Transfection ; Vimentin ; analysis ; genetics