Neural-cadherin expression associated with angiogenesis in non-small-cell lung cancer patients

An immunohistochemical analysis for E(epithelial)-cadherin and N(neural)-cadherin expression in relation to tumour angiogenesis was performed in 150 patients with nonsmall cell lung cancer (NSCLC). In all, 71 carcinomas (47.3%) were E-cadherin-negative. Epithelial-cadherin-negative tumours had lymph node metastases significantly more frequently than E-cadherin-positive tumours (P=0.0100). On the other hand, 46 carcinomas (30.7%) were N-cadherin-positive. Regarding tumour vascularity, there was no significant correlation between E-cadherin expression and tumour vascular. In contrast, the frequency of hypervascular tumours was significantly higher for N-cadherin-positive carcinomas than for N-cadherin-negative carcinomas (P=0.0373). Regarding prognosis, the 5-year survival rate of patients with E-cadherin-negative NSCLCs was significantly lower than that of patients with E-cadherin-positive NSCLCs (P=0.0146). In contrast, of the patients with large cell carcinomas, the 5-year survival rate of patients with N-cadherin-positive tumours was significantly lower than that of patients with N-cadherin-negative tumours (P=0.0013). A multivariate analysis demonstrated that E-cadherin status (P=0.0339) and tumour vascularity (P=0.0295) were significant indicators for survival. In conclusion, E-cadherin expression and tumour vascularity are significant prognostic factors of NSCLC patients. Furthermore, N-cadherin expression is associated with tumour angiogenesis, and its expression is one of prognostic factors of patients with large cell carcinomas. Thus, N-cadherin also might play a specific role in undifferentiated large cell carcinomas.     

钙黏附蛋白及降钙素在前列腺癌组织中的表达及意义

目的探讨前列腺癌浸润转移的机制以及上皮间质转化现象的意义。方法采用免疫组化法检测34份前列腺癌组织（观察组）和10份前列腺增生组织（对照组）中上皮性钙黏附蛋白（E-cadherin）、神经性钙黏附蛋白（N-cadherin）及降钙素表达。结果观察组E-cadherin、N-cadherin及降钙素阳性率分别为44.1%、67.6%、44.1%;对照组分别为90.0%、0.0%、10.0%;P均〈0.05。E-cadherin表达随肿瘤分化程度的降低而减少,与N-cadherin和降钙素表达呈负相关,N-cadherin与Calcitonin表达呈正相关,P均〈0.05。结论 E-cadherin、N-cadherin和降钙素与前列腺癌的发生、发展明显相关,可作为判断前列腺癌恶性进展的指标。     

Twist基因在胃癌中表达与EMT现象的研究

目的：研究Twist、E—cadherin、N—cadherin在胃癌组织中的表达及上皮间质转化（EMT）现象,探讨其与胃癌侵袭转移的关系。方法：分别采用逆转录聚合酶链反应（RTPCR）和免疫组化方法检测58例胃癌组织和对应癌旁组织中介导EMT发生的转录因子Twist、上皮性标记基因E—cadherin以及间质性标记基因Ncadherin的表达情况。结果：胃癌组织中Twist、Ecadherin以及Ncadherin蛋白阳性表达率分别为75．8％、36．2％、44．8％,癌旁组织分别为32．7％、91．3％、12．1％,3种蛋白在胃癌组织中及癌旁组织的表达差异均有统计学意义（P〈0．01或P〈0．05）。与癌旁组织相比,TwistmRNA和Ncadherin mRNA在胃痛组织中表达明显上凋,Ecadherin mRNA表达下调。结论：Twist介导的EMT发生可能与胃癌的侵袭转移有关。     

人口腔鳞状细胞癌组织中N-Cadherin蛋白的表达及临床意义

目的 探讨神经型钙黏附蛋白(N-cadherin)在人口腔鳞状细胞癌(OSCC)组织中的表达及其临床意义.方法 采用免疫组织化学方法 分别检测85例正常口腔上皮组织、62例癌旁不典型增生组织及85例OSCC组织中N-cadherin蛋白的表达,并分析其与临床病理学参数之间的关系.结果 N-cadhedn蛋白在OSCC组...     

Inhibition of N-cadherin and beta-catenin function reduces axon-induced Schwann cell proliferation

N-cadherin and beta-catenin are involved in cell adhesion and cell cycle in tumor cells and neural crest. Both are expressed at key stages of Schwann cell (SC) development, but little is known about their function in the SC lineage. We studied the role of these molecules in adult rat derived SC-embryonic dorsal root ganglion cocultures by using low-Ca(2+) conditions and specific blocking antibodies to interfere with N-cadherin function and by using small interfering RNA (siRNA) to decrease beta-catenin expression in both SC-neuron cocultures and adult rat-derived SC monocultures. N-cadherin blocking conditions decreased SC-axon association and reduced axon-induced SC proliferation. In SC monocultures, beta-catenin reduction diminished the proliferative response of SCs to the mitogen beta1-heregulin, and, in SC-DRG cocultures, beta-catenin reduction inhibited axon-contact-dependent SC proliferation. Stimulation of SC cultures with beta1-heregulin increased total beta-catenin protein amount, phosphorylation of GSK-3beta and beta-catenin presence in nuclear extracts. In conclusion, our findings suggest a previously unrecognized contribution of beta-catenin and N-cadherin to axon-induced SC proliferation.     

E-cadherin和N-cadherin在原发性肝细胞癌中的表达

目的探讨原发性肝细胞癌(HCC)中E-钙黏附素(E-cadherin)与N-钙黏附素(N-cadherin)的表达情况以及两者表达的相关性,寻找它们与HCC转移的关系。方法采用免疫组化两步法检测46例HCC组织和10例正常肝组织中E-cadherin和N-cadherin的表达。结果46例HCC中E-cadherin呈低表达的有34例(73.9%),N-cadherin呈低表达的有30例(65.2%);10例正常肝组织中两种钙黏附素均呈高表达;E-cadherin和N-cadherin的表达皆与HCC分化程度有关(P<0.05),两者之间的表达强度呈正相关(Spearman秩相关系数r=0.579,P<0.01);对比转移倾向高危组和低危组,E-cadherin及N-cadhein的表达强度组间差别显著(Wilcoxon秩和检验P<0.05),高危组中表达强度更低。结论E-cadherin和N-cadherin在HCC中的表达较正常肝组织低;E-cadherin与N-cadherin呈正相关;两种黏附素的低表达提示HCC的低分化和高转移倾向。     

Two-tiered coupling between flowing actin and immobilized N-cadherin/catenin complexes in neuronal growth cones

Neuronal growth cones move forward by dynamically connecting actin-based motility to substrate adhesion, but the mechanisms at the individual molecular level remain unclear. We cultured primary neurons on N-cadherin–coated micropatterned substrates, and imaged adhesion and cytoskeletal proteins at the ventral surface of growth cones using single particle tracking combined to photoactivated localization microscopy (sptPALM). We demonstrate transient interactions in the second time scale between flowing actin filaments and immobilized N-cadherin/catenin complexes, translating into a local reduction of the actin retrograde flow. Normal actin flow on micropatterns was rescued by expression of a dominant negative N-cadherin construct competing for the coupling between actin and endogenous N-cadherin. Fluorescence recovery after photobleaching (FRAP) experiments confirmed the differential kinetics of actin and N-cadherin, and further revealed a 20% actin population confined at N-cadherin micropatterns, contributing to local actin accumulation. Computer simulations with relevant kinetic parameters modeled N-cadherin and actin turnover well, validating this mechanism. Such a combination of short- and long-lived interactions between the motile actin network and spatially restricted adhesive complexes represents a two-tiered clutch mechanism likely to sustain dynamic environment sensing and provide the force necessary for growth cone migration.Growth cones are motile structures at the extremity of axons responsible for path finding and neurite extension during nervous system development and repair. Growth cones translate extracellular signals into directional migration through a coordinated regulation of cytoskeleton, adhesion, and membrane processes (1). At the cytoskeletal level, motility is generated by polarized actin treadmilling, which, together with myosin contraction, generates a continuous retrograde actin flow from the periphery to the base of growth cones (2–7). At the membrane level, adhesion proteins form dynamic bonds with immobilized extracellular ligands, allowing step-by-step locomotion (8).The molecular clutch model postulates that the mechanical coupling between ligand-bound transmembrane adhesion receptors and the actin flow allows traction forces to be transmitted to the substrate, resulting in local diminution of the retrograde flow and forward progression (9–11). Optical tweezers and flexible substrate experiments using microspheres coated with adhesion molecules revealed clutch-like mechanisms for integrins (12, 13), Ig cell adhesion molecules (14, 15), and cadherins (16, 17). However, the mechanism of clutch engagement at the individual molecular level remains elusive. For integrin-based adhesion, single-molecule tracking experiments suggested that talin and vinculin could switch between a state bound to flowing actin and a state bound to immobilized integrins (18, 19). For cadherin-based adhesion, biochemical experiments suggested that α-catenin could transit between being bound to actin or to the cadherin/β-catenin complex (20, 21), but a direct visualization of such behavior is lacking. In addition, vinculin, which can bind both actin and α-catenin, is recruited at cadherin-based intercellular junctions under mechanical force (22–24), but its dynamic behavior in growth cone migration is unknown.By combining spatially controlled adhesion in growth cones with single-molecule tracking, fluorescence recovery after photobleaching (FRAP) experiments, and computer simulations, we report that N-cadherin/α-catenin complexes, but not vinculin, are selectively trapped at N-cadherin micropatterns. In addition, 80% of actin molecules flow rearward, making transient pauses on the order of seconds with immobilized N-cadherin/α-catenin complexes, whereas 20% of confined actin molecules contribute to local actin enrichment. This association of short- and long-lasting individual bonds underlies the differential coupling between the actin motile machinery and substrate adhesions supporting growth cone migration.     

转录因子Twist及其相关因子N-cadherin在胰腺癌中的表达及意义

目的 探讨转录因子Twist及其下游相关因子N-cadherin在人胰腺癌组织中的表达及与肿瘤临床病理特征、患者预后的关系.方法 采用免疫组化MaxVision两步法分别检测62例胰腺癌组织和10例正常胰腺组织中Twist及N-cadherin的表达,分析二者表达与临床病理特征及患者预后的相关性.结果 Twist在胰腺癌组织的阳性表达率明显高于正常胰腺组织(96.8％比30.0％,P＜0.01),N-cadherin在胰腺癌组织的阳性表达率也明显高于正常胰腺组织(75.8％比0,P＜0.01),但两者的表达无明显相关性(r=0.100,P=0.441).Twist及N-cadherin表达与胰腺癌TNM分期、淋巴结转移、门静脉或神经浸润、肿瘤部位均密切相关(P值均＜0.05),与患者年龄、性别及肿瘤分化程度均无明显相关性(P值均＞0.05).胰腺癌患者术后生存期随Twist表达的增强而缩短,但与N-cadherin表达强度无明显相关性.TNM分期、Twist表达强度是影响胰腺癌患者预后的独立因素.结论 胰腺癌组织Twist及N-cadherin均高表达,其表达与胰腺癌的恶性生物学行为相关,Twist的异常表达可能是评估胰腺癌患者预后的潜在指标.     

上皮间质转化及CD146和N-cadherin在判定肺腺癌EGFR-TKI获得性耐药中的作用

目的 探讨上皮间质转化及CD146、N-cadherin判定肺腺癌表皮生长因子受体-酪氨酸激酶抑制剂（epidermal growth factor receptor-tyrosine kinase inhibitor,EGFR-TKI）耐药的价值。方法 肺腺癌患者10例均应用EGFR-TKI治疗,采用免疫组织化学法检测治疗前、后肺腺癌标本E-cadherin、vimentin、CD146及N-cadherin蛋白表达情况,采用图像分析系统检测各指标吸光度值。结果 EGFR-TKI治疗后肺腺癌组织E-cadherin蛋白表达水平（0.180±0.011）低于治疗前（0.231±0.012）,vimentin、N-cadherin与CD146蛋白表达水平（0.231±0.012,0.214±0.013,0.321±0.022）高于治疗前（0.165±0.012,0.174±0.013,0.161±0.022）（P〈0.05）。结论 EGFR-TKI耐药后肺腺癌产生上皮间质转化并使CD146、N-cadherin表达上调,E-cadherin、vimentin、CD146、N-cadherin可作为诊断肺腺癌EGFR-TKI耐药的分子标志物。