Objective To investigate the expression of c-met in tall cell variant of papillary thyroid carcinoma, and to compare it with other types of thyroid carcinoma and benign thyroid tissue. Methods The expressions of c-met in 60 cases of thyroid specimens were tested by immunohistochemical staining. Results The levels of expressed c-met in tall cell variant specimens were significantly higher than those in other types of papillary thyroid carcinoma and benign thyroid tissue. c-met expressions were significantly different in the following pairs of types: tall cell variant vs common papillary carcinoma of thyroid (P=0.000 1), tall cell variant vs follicular variant papillary thyroid carcinoma (P=0.000 1), and tall cell variant vs benign thyroid tissue (P=0.000 1). In addition, for all types of papillary carcinomas evaluated, c-met expression was significantly higher in specimens with extracapsular spread (P=0.010 0) and skeletal muscle invasion (P=0.020 0). Conclusion The high expression of c-met is a significant marker for tall cell variant papillary carcinoma of thyroid and its invasive behavior. This finding may explain the unusually aggressive behavior of this tumor and suggest a role for c-met in the early identification of patients with tall cell variant thyroid carcinoma.
Objective To study the expressions of Wnt5a, MMP2, and MMP14 in the primary lesions of gastric cancer and the influences on clinicopathologic features. Methods The expressions of Wnt5a, MMP2, and MMP14 in the specimens of 106 patients with gastric cancer and 39 patients from the adjacent normal gastric tissues were detected by immunohistochemical staining, χ2 test and non-parametric test were used to analyze the relationships among them and between them and their influences on the clinicopathologic features. Results Extensive expressions of Wnt5a, MMP2, and MMP14 were demonstrated in the gastric cancer, which were significantly higher than those in the normal gastric tissues respectively (Plt;0.05). Positive expression of Wnt5a was associated with larger tumor diameter, deeper depth of invasion, higher degree of regional lymph node metastasis, later TNM stage, and higher rate of lymph node metastasis (Plt;0.05). In addition, Wnt5a expression was also associated with lymphatic infiltration and vascular infiltration (Plt;0.05). The expressions of MMP2 and MMP14 were associated with lymphatic infiltration, but not with vascular infiltration. Higher expressions of MMP2 and MMP14 were correlated with deeper tumor invasion, higher degree of regional lymph node metastasis, later TNM stage, and higher rate of lymph node metastasis (Plt;0.05). In addition, higher expression of MMP2 possesed greater tumor diameter (Plt;0.05). Spearman rank correlation analysis revealed the positive relation between Wnt5a and MMP2 （rs=0.240, P=0.014）, Wnt5a and MMP14 （rs=0.251, P=0.010）, as well as MMP2 and MMP14 （rs=0.444, P=0.000）. Conclusion Higher expressions of Wnt5a, MMP2, and MMP14 seem to promote invasion and metastasis of gastric cancer, and there are positive relations among their expressions.
For an advanced elucidation of mechanisms of nm23-H1 suppressive effects on metastasis of primary hepatocellular carcinoma (HCC), it is necessary to investigate the correlation between nm23-H1 expression and relative factors involved in the HCC invasion. In present report, full-length cDNA of nm23-H1 was subcloned into pBKCMV vector and transfected into HCC cell line to observe its effects on invasion, cytosolic free Ca2+ and Nras mRNA expression. The results showed that lower expression of N-ras and higher cytosolic free Ca2+ in transfected cell line were detected, while the potential of invasion was depressed. It suggests that the suppressive effects on HCC metastasis might interact with intracellular signal transduction which is essential for stimulating cell invasion.
Objective To examine the effects of newly designed LY52 on the expression of matrix metalloproteinases and invasive ability of hepatocellular carcinoma HepG2 cells. Methods The effects of LY52 on the proliferations of HepG2 cells were detected by MTT assay. Gelatin zymography and Western blot were used to detect the effects of LY52 on matrix metalloproteinase-2 expression in the cell line. Transwell chamber assay was used to detect the effects of LY52 on the invasion of the cells. Results No obvious inhibitory or cytotoxicity effects of LY52 was found in lower concentrations (lt;200 μg/ml) of LY52. Gelatin zymography and Western blot showed that matrix metalloproteinase-2 expression were inhibited by LY52 in a dose-dependent manner in HepG2 cells. Furthermore, transwell chamber assay showed that LY52 could significantly inhibit the invasion of the cell line in a dose-dependent manner.Conclusion The results suggest that LY52 may inhibit the invasion of hepatocellular carcinoma cells by suppressing the matrix metalloproteinase-2 activity.
Objective To observe the effect of epidermal growth factor (EGF) on the proliferation, adhesion, invasiveness and the activation of nuclear factor-κB (NF-κB), matrix metalloproteinases (MMPs) expression and explore related mechanisms in pancreatic cancer cells. Methods Cell invasion assay, proliferation assay and adhesion assay were used to examine the proliferation, adhesion and invasiveness of pancreatic cancer cells, respectively. NF-κB activity was detected by electrophoretic mobility shift assay (EMSA), and MMPs protein and mRNA expressions were investigated by gelatin zymography, Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR). Results EGF increased the invasiveness of pancreatic cancer cell in a dose-dependent manner (P＜0.05), but did not affect cell proliferation or adhesion. The expressions of MMP-9 mRNA and protein significantly increased after induction by EGF and were highest when EGF concentration was 50 ng/ml, while there was no effect on the expressions of MMP-2 mRNA and protein. Furthermore, NF-κB activity increased with increased concentration of EGF in a concentration-dependent manner (P＜0.05). In addition, NF-κB activity and the expressions of MMP-9 mRNA and protein by pretreatment with both pyrrolidine dithiocarbamate (PDTC) and EGF decreased when compared that by pretreatment with EGF alone. The invasiveness of pancreatic cancer cell by pretreatment with both PDTC and EGF decreased when compared that by pretreatment with EGF alone and nothing (P＜0.05).Conclusion The findings indicate that the NF-κB-mediated MMP-9 induction is essential for EGF-induced invasiveness in pancreatic cancer cells, which can be inhibited by PDTC.
Objective To summarize the role of matrix metalloproteinases (MMPs) in occurrence and development of gastric cancer. Methods Domestic and international publications online involving MMPs of gastric cancer in recent years were collected and reviewed. Results The occurrence and development of gastric cancer was a multi-step and multi-factorial complicated progress, whose etiology and pathogenesis were still unclarified. MMPs were a class of proteolytic enzymes, which played an important role in the proliferation, metastasis, angiogenesis of gastric cancer and apoptosis of tumor cells and their surrounding normal cells by regulating the microenvironment of the growth of tumor. Conclusion MMPs promote the evolution of gastric cancer in variable ways, the mechanisms of which should be comprehended to provide a theoretical basis for the future treatment of gastric cancer.
ObjectiveTo explore the expression of MSI2 in gastric cancer and its association with clinical significance. MethodsThe expression level of MSI2 mRNA in gastric cancer tissues and para-carcinoma tissues was detected by Real-time PCR to explore its clinical significance. The expression level of MSI2 protein was detected by Western blotting. The prognosis of patients with the ratio of MSI2 mRNA expression level in gastric cancer tissues and adjacent normal tissues was more than 2 times and below 2 times were compared. ResultsThere was no significant difference between the expressions of MSI2 mRNA in cancer tissues and para-carcinoma tissues(P > 0.05). The expression level of MSI2 mRNA were associated with the invasion depth (P=0.017), TNM stage (P=0.028), differentiation (P=0.020), and size (P=0.030) of tumor, but no association with other clinical factors such as gender, age, and location were found. The overall survival of the patients with high expression of MSI2 mRNA was significantly shorter than that of the patients with low expression of MSI2 mRNA (χ2=4.221, P=0.040). ConclusionMSI2 expression is associated with the gastric cancer invasion, TNM stage and differentiation, and the patients with higher expression of MSI2 mRNA have poor prognosis, which makes it possible to be a potential therapeutic target.
ObjectiveTo investigate the expressions of Snail and VEGF gene in invasion ductal carcinoma tissues and analyze their clinicopathologic relationship. MethodsThe expressions of Snail and VEGF gene were detected on mammary gland hyperplasia (30 cases), intraductal breast cancer (30 cases), and invasion ductal carcinoma (70 cases) by in situ hybridization， to compare with the expression difference of the two genes in the different pathological changed tissues of mammary gland and among the clinicopathological facters of invasion ductal carcinoma as well as the relationship. ResultsThe expression rate of Snai mRNA in mammary gland hyperplasia， intraductal breast cancer, and invasion ductal carcinoma was 23.3% (7/30)， 46.7% (14/30), and 81.4% (57/70), respectively, there was statistical difference among them (χ 2=32.4, Plt;0.05)； The expression rate of VEGF mRNA in mammary gland hyperplasia， intraductal breast cancer, and invasion ductal carcinoma was 33.3% (10/30)， 50.0% (15/30), and 71.4% (50/70), respectively, there was statistical difference among them (χ 2=13.4, Plt;0.05). The expression rates of Snail mRNA and VEGF mRNA in lymphatic metatasis group were significantly higher than those in no lymphatic metatasis group 〔92.7% (38/41) vs. 65.5% (19/29)， χ 2=8.29, Plt;0.05； 85.4% (35/41) vs. 51.7% (15/29), χ 2=9.42, Plt;0.05， respectively 〕. The expression rates of Snail mRNA and VEGF mRNA in Ⅲ-Ⅳ stage of TNM clinical stage were significantly higher than those in Ⅰ-Ⅱ stage 〔939% (46/49) vs. 52.4% (11/21), χ 2=14.14， Plt;0.05； 81.6% (40/49) vs. 47.6% (10/21), χ 2=8.32， Plt;0.05〕. The expressions of Snail mRNA and VEGF mRNA were related to the expressions of ER, PR, HER-2, and vessel cancer embolus （Plt;0.01）. The expressions of Snail mRNA and VEGF mRNA were not related to age, tumor size, and histological grade (Pgt;0.05). There was a positive correlation between the expressions of Snail mRNA and VEGF mRNA （r=0.67， Plt;0.05）. ConclusionsThe overexpressions of Snail mRNA and VEGF mRNA in invasion ductal carcinoma has a synergetic effect on occurrence and development, therefore, combined detecting the expressions of Snail mRNA and VEGF mRNA are some significance to predict infiltration and metastasis of the invasion ductal carcinoma.
ObjectiveTo explore the effects of silencing the expression of ubiquitin-conjugating enzyme E2T (UBE2T) gene on proliferation, apoptosis, migration and invasion abilities of A549 cells.MethodsA549 cells were cultured in vitro. Three sets of shRNA-UBE2T plasmid vectors (UBE2T-shRNA1 group, UBE2T-shRNA2 group, UBE2T-shRNA3 group) and shRNA-NC (shRNA-NC group) were constructed, respectively. A549 cells were transfected with lipofection transfection. The cells transfected with empty vector were enrolled as control (control group). The transfection efficiency was detected by RT-PCR. The effects of silencing the expression of UBE2T gene on biological behaviors (proliferation, apoptosis, migration, and invasion) of lung cancer A549 cells were detected by clone formation assay, flow cytometry, Transwell assay and scratch test. The expression of proliferation and apoptosis related proteins, and expression of PI3K/AKT signaling pathway proteins were detected by Western blot. ResultsAfter transfection, expression level of UBE2T mRNA in UBE2T-shRNA1 group, UBE2T-shRNA2 group and UBE2T-shRNA3 group was significantly down-regulated (all P<0.05), whose down-regulation was the most significant in UBE2T-shRNA3 group (P<0.05). Compared with control group and shRNA-NC group, clone formation rate, number of invasion A549 cells, scratch healing rate, Ki67 expression, PCNA expression, p-PI3K/PI3K ratio and p-AKT/AKT ratio were significantly decreased in UBE2T-shRNA3 group (P<0.05), while A549 apoptosis rate, Bax/Bcl-2 ratio and cleaved caspase-3/caspase-3 ratio were significantly increased (P<0.05). There were no significant differences in the above indexes between control group and shRNA-NC group (P>0.05). ConclusionsThe shRNA interfering with UBE2T is reliable to construct the model of A549 cells with stable low-expression UBE2T. Down-regulation of UBE2T expression can promote apoptosis of A549 cells, inhibit their proliferation, invasion and migration abilities. The mechanism may be related to inhibiting the activation of PI3K/AKT signaling pathway.
ObjectiveTo summarize the relationship of microRNA (miRNA) to metastasis and invasion of breast cancer. MethodDomestic and international publications involving the relationship of miRNA to breast cancer were screened and reviewed. ResultsmiRNA played a key role in the process of breast cancer metastasis. According to its function, it could be distinguished from cancer-promoting gene (such as miR-21, miR-10b, etc.) to suppressor gene (such as miR-31, let-7, etc.). ConclusionThe more detailed experimental studies about the relationship of miRNA to metastasis and invasion of breast cancer need to be researched in order to provide a new method for the diagnosis and treatment of breast cancer metastasis and invasion.