Endometrial stem/progenitor cells and their role in the pathogenesis of endometriosis

Human endometrium regenerates on a cyclical basis each month, likely mediated by endometrial stem/progenitor cells. Several types of stem/progenitor cells have been identified: CD140b⁺CD146⁺ or SUSD2⁺ endometrial mesenchymal stem cells (eMSCs), N-cadherin⁺ endometrial epithelial progenitor cells (eEPs), and side population (SP) cells, a heterogeneous population predominantly comprising endothelial cells. eMSCs reside in a perivascular niche and likely mediate angiogenesis and stromal regeneration. Human eEPs are located in the bases of glands in the basalis and are likely more primitive than SSEA-1⁺ basalis epithelial cells. Endometrial stem/progenitor cells may contribute to the pathogenesis of endometriosis by their retrograde shedding into the pelvic cavity, either after menarche or as a result of neonatal uterine bleeding. eMSCs may have a role in the generation of progesterone-resistant phenotype of endometrial stromal fibroblasts (eSFs) in endometriosis. In future clinical practice, endometrial stem/progenitor cells may be used to establish diagnosis of endometriosis or as therapeutic targets.     

N-cadherin knock-down decreases invasiveness of esophageal squamous cell carcinoma in vitro

AIM： To examine the expressions of N-cadherin and E-cadherin in specimens of 62 normal esophageal epithela, 31 adjacent atypical hyperplastic epithelia and 62 esophageal squamous cell carcinomas （ESCCs）, and to investigate the roles of N-cadherin in the invasiveness of ESCC cell line EC9706 transfected by N-cadherin shRNA.
METHODS： PV immunohistochemistry was used to detect the expression pattern of N-cadherin and E-cadherin in specimens of 62 normal esophageal epithelia, 31 adjacent atypical hyperplastic epithelia and 62 ESCCs. The invasiveness of ESCC line EC9706 was determined by transwell assay after EC9706 was transfected by N-cadherin shRNA.
RESULTS： The positive rotes of N-cadherin decreased in the carcinoma, adjacent atypical hyperplastic and normal esophageal tissues （75.8%, 61.3% and 29.0%, P 〈 0.05）, respectively, while those of E-cadherin increased （40.3%, 71.0% and 95.2%, P 〈 0.05）. The increased expression of N-cadherin and decreased expression of E-cadherin were related to invasion, differentiation, and lymph node metastasis （P 〈 0.05）. The expression level of N-cadherin decreased in the N-cadherin knocked down cells, and the invasiveness of those cells decreased significantly as well. The number of cells which crossed the basement membrane filter decreased from 123.40 ± 8.23 to 49.60 ±6.80 （P 〈 0.05）.
CONCLUSION： E-cadherin and N-cadherin expression is correlated with the invasion and aggravation of ESCC. The down-regulation of N-cadherin lowers the invasiveness of EC9706 cell line.     

A Correlative Study of N-Cadherin Expression with Different Grades of Oral Squamous Cell Carcinoma Projecting as a Marker of Epithelial to Mesenchymal Transition in Tumor Progression

Background: Epithelial cells typically express E-cadherin where as N-cadherin expressed by mesenchymal cells.The epithelial to mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell-celladhesion, and gain migratory and invasive properties to become mesenchymal cells. EMT is typical for carcinoma cellsduring tumor progression and correlate with the local invasiveness and metastatic potential of the tumor. Oral squamouscell carcinoma is a malignant neoplasm arising from the mucosal epithelium of the oral cavity. It can be classifiedas well; moderate and poor depends on a tumor cells resemblance to its tissue of origin. Materials and Methods: Atotal of 130 cases of histopathologically diagnosed as OSCC were selected for the study, out of which 66,38 and 26were well, moderate and poorly differentiated respectively. One section was stained with Haematoxylin and Eosinand the other section for N-cadherin immunohistochemical study. Then the N-cadherin expression was correlatedhistopathologically with different grades of OSCC. Statistical analysis was carried out mainly by Chi-Square analysis.Results: Among the 66 cases of WDSCC mean value of N-cadherin expression was 1.79, 38 cases of MDSCC meanvalue of N-cadherin expression was 4.16 and among the 26 cases of PDSCC the mean value was 6.38.That means thevalue of N- cadherin expression was progressively increasing with decreased differentiation of the tumor cells. Thestatistical analysis also shown it was highly significant (P<0.001). Conclusion: A correlative study of N-cadherinexpression with different grades of OSCC will be useful to predict the state of tumor progression and also it may giveaccuracy for histopathogical grading of the tumor.     

苹果多糖抑制人结肠癌细胞SW-620转移的作用及机制研究

目的:研究苹果多糖对人结肠癌SW-620细胞侵袭与迁移的影响及相关机制。方法:培养人结肠癌SW-620细胞,分别加入苹果多糖 （0.1,0.3 mg/ml）24 h后,使用transwell小室、划痕实验观察苹果多糖对SW-620细胞侵袭与迁移的影响,以免疫印迹法检测细胞中E-cadherin,N-cadherin的表达变化。结果:苹果多糖可以有效地抑制SW-620细胞的侵袭与迁移,浓度依赖性地上调E-cadherin、下调N-cadherin的蛋白表达。结论:苹果多糖可有效地阻遏结肠癌细胞SW-620的侵袭与迁移,其可能机制与其升高E-cadherin、降低N-cadherin的表达水平有关。     

Snail及N-cadherin蛋白在骨肉瘤中的表达及其与预后的关系

目的观察Snail及N-cadherin蛋白在骨肉瘤中的表达,探讨其在骨肉瘤发生发展、浸润转移的作用及其与预后的关系。方法采用免疫组织化学SP法检测38例骨肉瘤组织、20例骨软骨瘤组织中Snail及N-cadherin蛋白的表达。结果(1)Snail、N-cadherin蛋白在骨肉瘤中表达均高于它们在骨软骨瘤组织中的表达,其差异有统计学意义(χ²=27.375,P<0.01;χ²=21.849,P<0.01);(2)Snail和N-cadherin蛋白与骨肉瘤的软组织浸润、Ennecking分期、肺转移有关(P<0.05), 而与性别、年龄、部位、Dahlin类型无关(P>0.05);Snail、N-cadherin蛋白在骨肉瘤中的表达呈正相关(r=0.421,P<0.05);(3)骨肉瘤中Snail、N-cadherin蛋白阳性患者生存率均明显低于阴性患者,其差异均有统计学意义(P<0.05)。结论骨肉瘤组织中Snail蛋白及N-cadherin蛋白的高表达,提示它对骨肉瘤的发生发展和浸润转移起重要作用并预示患者预后不良。     

芍药内酯苷调控NF-κB抑制卵巢癌转移的作用研究

目的:研究芍药内酯苷(albiflorin,AL)抑制人卵巢癌转移的作用及其潜在机制。方法:卵巢癌耐顺铂SKOV3/DDP细胞分为5组:AL 25,50,100μmol·L^-1组、18μmol·L^-1 NF-κB抑制剂SN50组和空白对照组。采用划痕试验检测AL对迁移的影响,采用流式细胞术检测AL对凋亡的影响,采用RT-qPCR和western blot检测AL对CDH1、CDH2和NF-κB mRNA和蛋白表达的影响。结果:AL各组均可明显抑制SKOV3/DDP细胞迁移,增加细胞凋亡,具有浓度依赖性(P<0.05,P<0.01)。随着AL浓度增加,其对CDH2和NF-κB的抑制作用,及其对CDH1的诱导作用均逐渐增强(P<0.05)。AL 100μmol·L^-1组抑制迁移、诱导凋亡和抑制CDH2和NF-κB mRNA和蛋白表达的作用与SN50组相当(P>0.05),诱导CDH1 mRNA作用弱于SN50组(P<0.05),但诱导CDH1蛋白表达的作用与SN50组相当(P>0.05)。结论:AL抑制SKOV3/DDP迁移作用可能与其诱导凋亡和CDH1表达,抑制CDH2和NF-κB表达有关。     

Loss of ephrin-A5 function disrupts lens fiber cell packing and leads to cataract

Cell-cell interactions organize lens fiber cells into highly ordered structures to maintain transparency. However, signals regulating such interactions have not been well characterized. We report here that ephrin-A5, a ligand of the Eph receptor tyrosine kinases, plays a key role in lens fiber cell shape and cell-cell interactions. Lens fiber cells in mice lacking ephrin-A5 function appear rounded and irregular in cross-section, in contrast to their normal hexagonal appearance in WT lenses. Cataracts eventually develop in 87% of ephrin-A5 KO mice. We further demonstrate that ephrin-A5 interacts with the EphA2 receptor to regulate the adherens junction complex by enhancing recruitment of beta-catenin to N-cadherin. These results indicate that the Eph receptors and their ligands are critical regulators of lens development and maintenance.     

RAMP2参与膀胱癌进展的机制研究

目的探讨受体活性调节蛋白2(RAMP2)参与膀胱癌进展的潜在分子机制。方法从TCGA数据库获得人膀胱癌组织mRNA表达谱,并将标本分成高表达和低表达RAMP2两组,通过基因富集分析(GSEA)探讨RAMP2参与膀胱癌进展的可能分子机制;通过对人膀胱癌组织中关键分子的免疫组织化学染色验证上述分析结果。结果GSEA分析结果表明上皮细胞间质转化(EMT)相关基因于RAMP2高表达组织富集。通过免疫组织化学对RAMP2及EMT标志蛋白E-钙黏素(E-cadherin)、N-钙黏素(N-cadherin)进行染色后发现,E-cadherin低表达及N-cadherin高表达均可预示膀胱癌患者不良预后,N-cadherin在膀胱癌组织中的表达与RAMP2表达具有相关性。结论RAMP2可能通过N-cadherin促进膀胱癌恶性进展。     

Cadmium induces N-cadherin cleavage via ERK-mediated γ-secretase activation in C6 astroglia cells

N-cadherin has known to be involved in tumor progression and metastasis. However, it is still obscure about the signaling pathway involving in the processing of N-cadherin. Thus, we examined which signaling pathway plays a major role in the processing of N-cadherin in C6 glioma cells following treatment of cadmium (Cd), a highly ubiquitous heavy metal. A cleavage product of N-cadherin, N-cad/CTF2 was observed by the treatment of Cd to C6 cells in a time and concentration-dependent manner. The production of N-cad/CTF2 was inhibited by pretreatment of γ-secretase inhibitors or siRNA transfection of nicastrin, indicating that γ-secretase is involved in the cleavage. Interestingly, Cd could activate both ERK and JNK signaling pathways in C6 cells; however, γ-secretase-mediated N-cad/CTF2 production by Cd was completely blocked by MEK1/2 inhibitors PD184352 and U0126, but not by a JNK inhibitor SP600125, demonstrating that the ERK signaling pathway plays a major role in the cleavage. In addition, pretreatment of an antioxidant or Ca²⁺ blocker blocked the production of N-cad/CTF2 by Cd together with the inhibition of ERK1/2 phosphorylation. Collectively, these results suggest that Cd increases intracellular Ca²⁺ or ROS, which induces γ-secretase-dependent N-cad/CTF2 production via the activation of the ERK signaling pathway in C6 glial cells.