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.
ObjectiveTo study the relationship between mesenchymal transition epithelial (EMT) and the occurrence, development, invasion, and metastasis of gastric cancer, and to seek to block the EMT process so as to achieve the purpose of treating tumor. MethodsThe literatures of EMT, signal pathway, and gastric cancer were analyzed by querying the PubMed. ResultsThe function and regulation mechanism of EMT is closely related to the development of gastric cancer, in the growth and proliferation of gastric cancer, tumor invasion and metastasis through a variety of signaling pathways play a role, with a great clinical application prospects. ConclusionsEMT and tumor metastasis is very close, almost involved in every process of metastasis. It is necessary to further study the relationship between EMT and cancer, including gastric carcinoma metastasis. A new way for the treatment of human gastric cancer.
ObjectiveTo investigate the relationship of epithelial mesenchymal transition (EMT) related proteins expressions in invasive ductal carcinoma of breast to its clinicopathologic features and prognosis. MethodsThe expressions of EMT related proteins (Vimentin, E-cadherin, and MMP2) in the 118 cases of invasive ductal carcinoma of breast and 30 cases of corresponding normal breast tissues adjacent to cancer were detected by immunohistochemistry. The relationship of EMT related proteins expressions to age, tumor site, tumor size, lymph node metastasis, histological grade, TNM stage or prognosis of the patients with invasive ductal carcinoma of breast was analyzed. Results①The positive rates of the Vimentin protein and MMP2 protein in the invasive ductal carcinoma of breast were significantly higher than those in the corresponding normal breast tissues adjacent to cancer﹝Vimentin protein: 50.8% (60/118) versus 10.0% (3/30), P < 0.05; MMP2 protein: 63.6% (75/118) versus 6.7% (2/30), P < 0.05﹞, the positive rate of E-cadherin in the invasive ductal carcinoma of breast was significantly lower than that in the corresponding normal breast tissues adjacent to cancer ﹝56.8% (67/118) versus 93.3% (28/30), P < 0.05﹞.②The positive rate of the Vimentin protein expression in the invasive ductal carcinoma tissue was positively related with the lymph node metastasis and TNM staging (rs=0.346, P < 0.05; rs=0.231, P < 0.05). The positive rate of the E-cadherin or MMP2 protein expression was negatively or positively related with the tumor size, lymph node metastasis, histological grade, and TNM stage (E-cadherin: rs=-0.444, P < 0.05; rs=-0.493, P < 0.05; rs=-0.323, P < 0.05; rs=-0.474, P < 0.05. MMP2: rs=0.361, P < 0.05; rs=0.434, P < 0.05; rs=0.396, P < 0.05; rs=0.376, P < 0.05).③The Kaplan-Meier survival curve analysis showed that the positive expressions of Vimentin and MMP2 were stronger, the tumor free survival time was shorter (P < 0.05), and the positive expression of E-cadherin was stronger, the tumor free survival time was longer (P < 0.05). ConclusionJoint detection of EMT related proteins (Vimentin, E-cadherin, MMP2) of invasive ductal carcinoma tissue of breast could predict the pathological grade and clinical stage, as well as effective prognosis of patients with invasive ductal carcinoma of breast in clinical.
ObjectiveTo investigate that the TGF- beta/Smad signaling pathway mediated epithelial mesenchymal transition (EMT) in trachea stenosis after transplantation. Methods180-220 g male rats (n=50) were randomly divided into a control group and an experimental group. no surgical operation rats were in the control group. tracheal transplantation rats (Wistar-SD rat) were in the experimental group. Graft specimens were obtained in rats on 3,7,10,14,35,90 days after operation. HE staining is used to explain the fibrosis degree of tracheal stenosis. The fibrosis degree of tracheal stenosis was detected by calculating the fibrosis rate. Immunohistochemical staining was used to detect transplanted tracheal, such as EMT related molecules E-cadherin, vimentin, alpha-SMA expression, p-Smad2/3 expression and transcription factor ZEB1, Snail1 expression in tracheal graft specimens. ResultsHE staining showed that the tracheal fibrosis rate of the control group was 0.171±0.020, fibrosis rate was 0.537±0.013 (P < 0.01) on the third day after transplantation. The result of immunohistochemical staining showed that vimentin positive epithelial cells increased significantly (P < 0.05). E-cadherin expression significantly reduced (P < 0.05). Compared with the control group, TGF- beta expression increased (P < 0.05) in the experiment group. Compared with the control group, the expression of p-Smad2/3, the transcription factor ZEB1 and Snail1 significantly increased (P < 0.05) in the experiment group. ConclusionMechanism of tracheal stenosis may be due to EMT. At the same time, TGF- beta/Smad signaling pathway and transcription factor ZEB1, Snail1 may regulate the EMT.
ObjectiveTo investigate the effects of ezrin on transforming growth factor beta (TGF-β) mediated epithelial mesenchymal transition (EMT). MethodsHuman bronchial epithelial 16HBE cells were stimulated by TGF-β to induce EMT. The mRNA and protein levels were analyzed by RT-PCR and Western blot. Lentivirus (LV)-Ezrin-shRNA was employed to investigate the effects of ezrin deficiency on cell morphology and expressions of EMT associated biomarkers including E-cadherin, vimentin, and alpha smooth muscle actin (α-SMA). The effects of recombinant ezrin protein on 16HBE were also examined. ResultsThe expression of ezrin was down-regulated in 16HBE activated by TGF-β. Due to ezrin depletion, the cell morphology changed from a typical multilateral paving stone-like appearance to a mesenchymal-like fusiform appearance along with the decreased expression of epithelium biomarker E-cadherin and the increased mesenchymal cell markers, vimentin and α-SMA. Recombination protein ezrin increased the expression of E-cadherin whilst reducing vimentin and α-SMA. ConclusionTGF-β promotes EMT of 16HBE cells at least partly via inhibiting the expression of ezrin.
ObjectiveBy intervening with gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, to explore the downstream signaling pathway of the transcription factor forkhead box O3a (Foxo3a) in C57BL/6 mice who are induced to pulmonary fibrosis with bleomycin, as so to illuminate the possible mechanism of Foxo3a in epithelial-mesenchymal transition (EMT) of pulmonary fibrosis.MethodsThirty C57BL/6 mice aged 6 weeks in half genders were randomly divided into a control group, a bleomycin group and a gefitinib group. The mice in the control group were injected with saline via trachea. The mice in the bleomycin group were injected with bleomycin at a dose of 3 mg/kg via trachea. The mice in the gefitinib group were injected with bleomycin at a dose of 3 mg/kg via trachea and then gastrically perfused with gefitinib (20 mg·kg–1·d–1). 14 days after the treatment, all mice were killed and lung tissue specimens were collected for further detection. Lung tissue sections were stained with hematoxylin eosin and Masson’s trichrome. The mRNA levels of α-smooth muscle actin (α-SMA), E-cadherin, high mobility group protein box 1 (HMGB1), Foxo3a, FoxM1 and Snail1 in the lung tissues were detected by RT-PCR. The protein expressions of α-SMA, E-cadherin, HMGB1, phospho-Foxo3a (p-Foxo3a), Foxo3a, FoxM1 and Snail1 in the lung tissues were determined by western blot.ResultsThe scores of lung inflammation and fibrosis were evidently decreased in the gefitinib group compared with that in the bleomycin group (P<0.01). Compared with bleomycin group, the mRNA level of α-SMA, Snail1 (P<0.01) and HMGB1 (P<0.05) were declined, but mRNA level of E-cadherin (P<0.01), Foxo3a and FoxM1 (P>0.05) were ascendant in the gefitinib group. Meanwhile, western blot analysis showed reduced protein expressions of α-SMA (P<0.05), Snail1(P<0.01), HMGB1 (P<0.05) and p-Foxo3a/Foxo3a (P<0.01) in lung tissues, while expressions of E-cadherin (P<0.05), Foxo3a and FoxM1 proteins (P>0.05) were increased in the gefitinib group.ConclusionsIncreased activity of Foxo3a can down-regulate Snail1, which decreases the expression of α-SMA and increases the expression of E-cadherin, thereby attenuating bleomycin-induced pulmonary fibrosis in mice.