尿激酶型纤溶酶原激活物及其特异受体和抑制物与肺癌的浸润转移

研究尿激酶型纤溶酶原激活物(uPA)及其特异受体(uPA-R)和抑制物(PAI-1、PAI-2)在肺癌浸润转移中的作用.应用RIA分别对67例经组织病理确诊的各期肺癌和30例肺部相关炎症患者及30名健康献血者进行了相应的检测.结果显示,小细胞肺癌Ⅱ期和Ⅲ期患者血浆中uPA、uPA-R、PAI-1水平显著升高(P＜0.001),而PAI-2的水平逐渐降低;腺癌、鳞癌伴有浸润主支气管及肺门淋巴结者uPA、uPA-R与PAI-1水平亦显著升高(P＜0.001);周围型肺癌未见淋巴结受侵者uPA、uPA-R、PAI-1与PAI-2水平异常升高.uPA、uPA-R与PAI-1在肺癌中水平明显升高,并与肺癌的浸润转移相关密切,可作为肿瘤患者早期诊断、预后评估的有力指标.     

uPA与NF-κB p65在乳腺癌组织表达的相关性研究及临床病理意义

目的：探讨尿激酶型纤溶酶原激活物（uPA ）基因与NF-κB p65在乳腺癌组织表达的相关性及临床病理意义。方法：采用实时荧光定量PCR法（FQ-PCR）检测了46例乳腺癌及其正常组织中的uPA mRNA（单位:2-△△Ct）及免疫组化检测NF-κB p65的表达。结果：乳腺癌 组织中均可检测到uPA mRNA表达，以2-△△Ct≥2为阳性标准，63％（29/46例）的乳 腺癌中uPA基因表达阳性；T/A 2-△△Ct值在不同NF-κB表达状态、肿瘤最大径及淋 巴结阳性数分组中，差异显著，P值分别为＜0.01和＜0.05；进一步经相关分析显示 ，uPA基因表达值与NF-κB表达状态、肿瘤最大径相关，r分别为0.451、0.512，均 P＜0.01；在患者年龄、肿瘤组织学类型及有无远处转移分组中，uPA基因表达未发现显 著性差异。结论：乳腺癌组织中uPA mRNA含量明显增高，并且与NF-κB 表达、肿瘤大小及淋巴结阳性数目有关。     

登革2型病毒调控血管内皮细胞纤溶系统相关蛋白的表达

目的观察登革2型病毒（DV2）对人脐静脉血管内皮细胞（HUVEC）表达组织纤溶酶原激活物（tPA）和纤溶酶原激活物抑制物1（PAI-1）的影响。方法应用胰酶消化分离HUVEC并进行传代培养，用生长良好的第2．3代细胞进行试验。用cell counting kit-8（CCK-8）测定DV2感染后细胞活性变化；发色底物法测定感染DV2组和对照组培养液中tPA、PAI-1活性；RT-PCR检测细胞内tPA和PAI-1 mRNA水平。结果DV2感染对细胞活力的影响与对照组相比差异无统计学意义。感染DV2组培养液中tPA活性在12～72h显著升高（P〈0．05）；DV2诱导HUVEC表达tPA mRNA的水平显著上调，12h达到峰值，以后渐降，72h mRNA表达水平仍高于对照组（P〈0．01）。而DV2感染组培养液中PAI-1活性和PAI-1 mRNA的表达与对照组比较差异无统计学意义（P〉0．05）。结论DV2感染可显著上调HUVEC的tPA mRNA转录，增强内皮细胞tPA蛋白的分泌，而不影响PAI-1 mRNA的转录或改变内皮细胞PAI-1的分泌。结果提示DV2可活化但并不损伤内皮细胞，诱发内皮细胞增强表达纤溶酶原激活物而致使纤溶系统失衡，引起纤溶亢进，这可能是诱发DHF／DSS患者急性期出血、低血容量性休克等体征的主要因素之一。     

肝素对大鼠Thy-1肾炎u-PA/PAI-1表达的影响

目的：研究尿激酶型纤溶酶原激活物／Ⅰ型纤溶酶原激活物抑制因子（u-PA/PAI-1)在大鼠Thy-1肾炎病变进展过程中的变化，以及肝素对其表达的影响。方法：以抗Thy-1单抗成功制备大鼠Thy-1肾炎模型，并用肝素对其进行治疗，分别于1、3、7、14、21、28d处死动物并分别取其肾皮质。应用RT－PCR及Western blot方法检测肾皮质u-PA/PAI-1 mRNA及蛋白表达的变化，以观察肝素对其表达的影响。结果：RT－PCR法显示肾炎模型组（G组）于3－28d的肾皮质u-PA mRNA和3－21d的肾皮质PAI－1 mRNA的表达均高于对照组（P＜0.05或P＜0.01)；肝素治疗组（H组）仅21d时肾皮质u-PA mRNA的表达高于G组（P＜0.05)，而PAI-1 mRNA的表达于3－28d时均低于G组（P＜0.05)。Western blot结果显示3－28d时，G组u-PA和PAI－1蛋白表达量高于对照组（P＜0.05或P＜0.01)，这与RT－PCR检测结果相似；H组肾皮质u-PA蛋白表达量与G组相比差异无显著性，而3－21d时PAI－1蛋白表达量均低于G组（P＜0.05或P＜0.01)。结论：大鼠Thy-1肾炎肾皮质u-PA与PAI－1的表达均随肾小球病变的进展而增强，肝素治疗可能通过干扰或抑制u-PA和PAI－1的表达而发挥其治疗作用。     

肝癌患者组织中凝血及纤溶因子的基因表达检测与分析

目的:检测组织因子（TF）、尿激酶型纤溶酶原激活物（uPA）及其受体（uPAR ）mRNA在肝细胞癌组织中的表达并探讨其临床意义。 方法:利用RT-PCR法分别检测27例肝细胞癌、癌旁及27例正常肝组织中TF、uPA、uPA mRNA表达阳性率及相对表达强度，并结合临床病理资料进行分析。 结果:TF、uPA、uPAR在肝细胞癌组织中阳性率及相对表达强度分别为62.96%（17/27）、70.37%（19/27）、77.78%（21/27）；0.567±0.268、0.964±0.458、0.784±0.322,均显著高于癌旁组织及正常组织，差异显著(P<0.05)。3者在肝癌组织中相对表达强度与肿瘤大小及部分侵袭转移指标有关，其中TF mRNA表达强度在肝内及肝外转移及门脉癌栓组高于无肝内及肝外转移及无门脉癌栓组(P<0.05) ，uPA mRNA在有包膜侵润、肝内转移及门脉癌栓组高于无包膜侵润、无肝内转移及门脉癌栓组(P<0.05)；uPAR mRNA在有肝内转移及门脉癌栓组高于无肝内转移及门脉癌栓组(P<0.05)。经Pearson检验肝细胞癌患者TF、uPA和uPAR mRNA表达呈正相关［TF-uPA：r=0.373(P<0.01)，TF-uPAR：r=0.534(P<0.01)，uPA-uPAR：r=0.365 (P<0.01)］。 结论:肝细胞癌组织中TF、uPA及uPAR的mRNA显著升高并与部分侵袭转移指标有关，提示3者可能在肝细胞癌的发生及侵袭转移起协同作用。     

肝纤维化时肝脏OPN和PAI-1的表达变化

目的:研究骨桥蛋白(OPN)及纤溶酶原激活物抑制物(PAI-1)的表达特征及其在肝纤维化时的变化。方法:采用二甲基亚硝胺制作大鼠肝纤维化模型,大鼠肝脏常规HE和天狼猩红染色,采用SABC法做免疫组织化学染色及Western blotting检测OPN和PAI-1蛋白表达,抽提肝组织总RNA,RT-PCR检测OPN mRNA表达。结果:正常大鼠肝组织OPN和PAI-1表达极弱,肝纤维化大鼠肝脏中OPN表达增强,阳性信号散在或弥漫性分布,主要见于小叶内中央静脉周围、纤维间隔内以及周围巨噬细胞胞浆、枯否氏细胞、汇管区的部分肝细胞、肝窦壁内皮细胞。PAI-1在肝纤维化大鼠肝组织汇管区、肝细胞变性坏死处,肝窦周Disse间隙及毗邻以上部位的肝细胞,组织纤维间隔处及其外周细胞亦见阳性染色。Western blotting检测正常大鼠肝脏OPN的蛋白表达极低,肝纤维化组OPN的蛋白表达较正常组显著增强(P0.01)。与正常组比,肝纤维化组PAI-1表达也显著增强。RT-PCR检测结果显示,正常大鼠肝脏OPN mRNA表达极低,肝纤维化大鼠肝脏OPN mRNA的表达明显增强(P0.05)。研究结果证明,肝纤维化时大鼠肝组织OPN及PAI-1的表达水平显著增高。结论:肝纤维化时大鼠肝组织OPN及PAI-1的表达水平显著增高,OPN可能会促进PAI-1的高表达,从而抑制ECM降解、加速肝纤维化进程。     

不饱和脂肪酸影响HepG-2细胞PAI-1表达的机制初探

目的：探讨不饱和脂肪酸对HepG-2细胞纤溶酶原激活物抑制剂-1(PAI-1)表达的影响及其机制。方法： 以发色底物法检测PAI-1活性，RT-PCR法检测PAI-1 mRNA水平；构建两个含不同片段缺失的PAI-1启动子序列控制表达的氯霉素转移乙酰酶（CAT）报告基因质粒，转染HepG-2细胞，ELISA法检测CAT表达量。结果： 油酸、亚油酸诱导下HepG-2细胞PAI-1mRNA表达及蛋白活性显著高于对照组；共转染过氧化体增殖物激活型受体表达质粒（PPARα-pSG5）PAI-1转录活性显著增加；转染NF-κB样蛋白结合序列缺失的重组质粒，亚油酸诱导下PAI-1转录活性显著增加，而转染VLDL/脂肪酸反应元件缺失的重组质粒则无显著变化。结论： 不饱和脂肪酸增强HepG-2细胞PAI-1 mRNA表达及活性；PPARα可能是其上调PAI-1表达所涉及的转录因子之一，且VLDL/脂肪酸反应元件在该调控中具有重要作用，但可能并不涉及NF-κB信号转导途径。     

HMGB1与胃癌组织血管形成的关系及其临床意义

目的 确定高迁移率族蛋白B1与胃癌组织血管生成之间的联系,筛选胃癌诊断和治疗的靶点。方法 收集2008年6月~2016年6月怀化市第一人民医院病理科正常胃、胃癌旁、胃癌癌组织蜡块共105例,采用常规HE染色（苏木素-伊红）、免疫组织化学染色（链霉菌抗生物素蛋白-过氧化物酶连结法-SP法）,检测正常胃组织、胃癌旁组织及胃癌组织中HMGB1的表达情况、检测人造血祖细胞抗原（CD34）的表达情况来反映正常胃组织、胃癌旁组织及胃癌组织中的微血管密度（MVD）,统计学分析HMGB1的表达与胃癌组织MVD之间存在的相关性。结果 正常胃组织HMGB1的阳性表达率低,胃癌癌旁组织HMGB1的阳性表达率增高、胃癌组织中HMGB1的阳性表达率最高,在三种组织中HMGB1的表达存在差异（P＜0.05）;HMGB1的表达水平与MVD表现出正相关性（r=0.205,P＜0.05）。结论 HMGB1在胃组织、胃癌旁组织、胃癌组织中的表达呈阶梯型增高,胃癌组织中HMGB1的表达水平与组织MVD成正相关性。     

新生大鼠缺氧缺血性脑损伤tPA、PAI-1表达的动态变化

目的:观察新生大鼠缺氧缺血性脑损伤(HIBD)中组织型纤溶酶原激活物(tPA)和1型纤溶酶原激活物抑制剂(PAI-1)表达变化的规律,探讨纤溶系统在缺氧缺血性脑损伤中的作用。方法:7日龄SD新生大鼠96只,随机分为2组:缺氧缺血性脑损伤组和假手术组。两组动物模型制备成功后3、6、12、24、36、48、72、96小时断头取脑,应用免疫组织化学及原位杂交方法检测缺氧缺血性脑损伤不同时间点t-PA、PAI-1表达的变化。结果:假手术组新生大鼠各脑区均有tPA、PAI-1蛋白及mRNA的弱表达,缺氧缺血性脑损伤组不同时间点t-PA、PAI-1二者表达呈不同的动态变化:tPA蛋白及mRNA 3小时开始表达增强,主要见于皮质和海马,神经元表达明显,血管表达较弱,48小时神经元及微血管内皮表达明显增强,72小时神经元表达明显减弱,微血管内皮见有明显阳性表达,之后表达减弱,3～96小时各时间点阳性着色神经元数目显著高于假手术组;PAI-1蛋白及mRNA 12小时表达有所增强,神经元和微血管内皮表达增多,72小时达高峰,12～96小时各时间点阳性着色神经元数目显著高于假手术组。结论:tPA和PAI-1参与HIBD的发病机制。     

uPA系统与神经胶质瘤局部侵袭

uPA系统包括尿激酶型纤溶酶原激活物（urokinase plasminogen activator, uPA）、 尿激酶型纤溶酶原激活物受体（urokinase plasminogen activation receptor, uPAR）和纤溶酶原激活物抑制剂(plasminogen activator inhibitor, PAI),它们参与了多种人类恶性肿瘤的局部侵袭和转移,是目前肿瘤治疗重要的分子靶点。uPA能激活纤溶酶原降解细胞外基质与基底膜,uPAR则能显著提升uPA的激活纤溶酶原的功能,两者结合能够增强肿瘤的侵袭性与转移能力。PAI主要通过促进血管内皮生长因子（vascular endothelial growth factor,VEGF）的表达,促进新生血管的形成,从而促进肿瘤的局部侵袭,但PAI又可通过抑制uPA-uPAR复合体的生物学活性来抑制肿瘤的局部侵袭。神经胶质瘤是最常见的颅内肿瘤,很少转移到颅外,局部侵袭是其预后不良的主要原因。近年来发现uPA系统的表达水平与神经胶质瘤的恶性程度呈正相关。本文综述了uPA系统对神经胶质瘤局部侵袭的影响及其在治疗中的意义。     

Prognostic relevance of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitors PAI-1 and PAI-2 in gastric cancer

Expression of urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1) and plasminogen activator inhibitor-2 (PAI-2) was evaluated in 125 surgically resected gastric cancers by immunohistochemical analysis. Tissue was stained immunohistochemically with a monoclonal antibody against human uPA and monoclonal antibodies against human PAI-1 and PAI-2. In addition, DNA ploidy patterns were determined by cytofluorometer after staining with propidium iodide. We found that 82 (66%) of the 125 gastric cancers expressed uPA as diffuse cytoplasmic staining, as intensely outlined luminal borders. PAI-1 expression was observed in 62 (50%) of 125 gastric cancer as a fine, diffuse and granular pattern in the cytoplasm. PAI-2 expression was observed in 65 (52%) of the 125 gastric cancers as a diffuse cytoplasmic staining. uPA-positive tumours showed a higher incidence of infiltration, lymph node metastasis and peritoneal dissemination than uPA-negative ones. Patients with uPA-positive tumours proved to have a significantly poorer prognosis than those with negative ones. PAI-1-negative tumours showed a higher incidence of liver metastasis and carried a poorer prognosis than PAI-1-positive ones. There was no significant correlation between uPA or PAI-1 expression and DNA ploidy patterns. Conversely, there was no significant relationship between PAI-2 expression and clinicopathological parameters and prognosis. According to the expression of uPA and PAI-1 status, groups of 19 uPA(–)/PAI-1(–), 44 uPA(+)/PAI-1(–), 23 uPA(–)/PAI-1(+) and 39 uPA(+)/PAI-1(+) were subdivided. Tumours with UPA(+)/PAI-1(–) had a significantly higher incidence of liver metastasis, lymph node metastasis and serosal invasion than the other groups of tumours. Patients with uPA(+)/PAI-1(–) tumours had a significantly poorer prognosis than those with uPA(–)/PAI-1(+) tumours. These results indicate that uPA expression is a useful biological prognostic indicator, and that uPA and PAI-1 may play an important part in the tumour progression and metastasis in gastric cancer.     

胃癌组织中尿激酶型纤溶酶原激活剂及其受体基因表达和临床意义

目的：研究尿激酶型纤溶酶原激活剂（ｕＰＡ）及其特异受体（ｕＰＡＲ）与胃癌的关系及其在胃癌浸润转移中的作用。方法：采用ｃＤＮＡ－ｍＲＡＮ原位分子杂交技术,分别检测了６４例胃癌及其癌旁组织中ｕＰＡ和ｕＰＡＲｍＲＮＡ表达情况,同时结合病人的临床生物学指征进行分析。结果：癌与癌周比较,ｕＰＡ和ｕＰＡＲｍＲＮＡ阳性表达率明显升高,Ｐ〈０．００１。在伴有淋巴结转移的病例中,ｕＰＡ和ｕＰＡＲ阳性例数分别为１９／２９和２４／２９,与无转移的１０／３５和１３／３５相比,Ｐ分别〈０．０１和〈０．００１。在浸润到肌层、浆膜层的病例中ｕＰＡ和ｕＰＡＲ阳性例数分别为２５／３８和３０／３８,与浸润到粘膜和粘膜下层的４／２６例和７／２６相比,Ｐ均〈０．００１。在ｕＰＡ和ｕＰＡＲ同时阳性的病例中,伴有淋巴结转移和浸润到肌层以下的分别占１５／２     

Expression of urokinase-type plasminogen activator,its receptor,and its inhibitor in gastric adenocarcinoma tissues.

The plasminogen and plasmin system, which is mainly regulated by urokinase-type plasminogen activator (uPA), its receptor (uPAR) and its inhibitor (PAI-1), is generally believed to play a role in cancer invasion and metastasis. This study was conducted to investigate the role of uPA, uPAR and PAI-1 in the invasion and metastasis of gastric adenocarcinoma. The expression of mRNAs for uPA and PAI-1 was determined by Northern blot analysis in nine primary gastric cancer tissues, nine paired metastatic lymph nodes and normal gastric mucosa. The mRNA of uPA was not or faintly detected in normal mucosa, while the expression was increased in both primary gastric cancer tissues and metastatic lymph nodes to a similar degree. The mRNA expression for PAI-1 in the gastric cancer tissues was not different from that in the paired metastatic lymph nodes and normal mucosae. uPAR was determined by immunohistochemical staining, demonstrating that five (56%) and six (67%) out of nine primary gastric cancer tissues and nine paired metastatic lymph nodes were positive, respectively and the intensity was stronger in metastatic lymph nodes. The results support the concept that most gastric cancer cells may have an innately moderate level of uPA and uPAR, and that increase of uPAR expression can be considered to be closely associated with cancer invasion and metastasis.     

Signalling networks associated with urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 in breast cancer tissues: new insights from protein microarray analysis

The urokinase-type plasminogen activator (uPA) and the main uPA inhibitor PAI-1 play important roles in cell migration and invasion in both physiological and pathological contexts. Both factors are clinically applicable predictive markers in node-negative breast cancer patients that are used to stratify patients for adjuvant chemotherapy. In addition to their classical functions in plasmin regulation, both factors are key components in cancer-related cell signalling. Such signalling cascades are well described in cell culture systems, but a better understanding of uPA- and PAI-1-associated signalling networks in clinical tissues is needed. We examined the expression of uPA, PAI-1, and 21 signalling molecules in 201 primary breast cancer tissues using protein microarrays. Expression of uPA was significantly correlated with the expression of ERK and Stat3, while expression of PAI-1 was correlated with the uPA receptor and Akt activation, presumably via integrin and HER-receptor signalling. Analysis of uPA expression did not reveal any significant correlation with staging, grading or age of the patients. The PAI-1 expression was correlated with nodal stage. Network monitoring for uPA and PAI-1 in breast cancer reveals interactions with main signalling cascades and extends the findings from cell culture experiments. Our results reveal possible mechanisms underlying cancer development.     

Plasminogen activator inhibitor-1 as a measure of vascular remodelling in breast cancer

The generation of urokinase plasminogen activator (uPA) by tumours is an important pathway for neoplastic cell invasion and metastasis. Indeed in several tumour types, elevated levels of uPA, its receptor (uPAR) or its inhibitor plasminogen activator inhibitor-1 (PAI-1) is associated with a poorer prognosis. Since endothelial cells also use this proteolytic system to remodel the extracellular matrix during angiogenesis and since angiogenesis, as assessed by microvessel density, is also a predictor of patient survival, this study was designed to investigate the relationship between angiogenesis and the urokinase system in breast tumours. The aims were to assess whether the uPA, uPAR and/or PAI-1 correlates with angiogenic activity and could therefore be a useful objective clinical measure of tumour neovascularization; and to clarify whether the poor outcome associated with high levels of the urokinase system is due to its association with angiogenesis. The study also sought to examine the relationship between the uPA system and vessel remodelling using loss of a basement membrane epitope (LH39) normally associated with established capillaries. The cytosolic levels of uPA, PAI-1 and uPAR were therefore measured by enzyme linked immunoabsorbent assay, together with tumour vascularity, in 136 well-characterized invasive breast carcinomas. There were significant relationships between uPA and uPAR (Spearman r=0.37, p<0.0001), uPA and PAI-1 (Spearman r=0.19, p=0.03) and between uPAR and PAI-1 (Spearman r=0.23 p=0.01). A significant correlation was also observed between PAI-1 and vessel remodelling (Spearman r=0.34, p=0.04), patient age (p=0.01), nodal status (p=0.047) and tumour grade (p=0.04), but no association between tumour vascularity and PAI (p=0.96), uPA (p=0.69) or uPAR (p=0.81) was present. No significant association was seen between any of the urokinase variables and expression of the angiogenic factor thymidine phosphorylase. Furthermore, no significant associations were found between any of the studied parameters and overall survival in a univariate analysis of the cancer patients. A multivariate Cox proportional hazard model of overall survival showed that uPA (p=0.15), but not uPAR (p=0.52) or PAI-1 (p=0.61), gave no additional prognostic information. These findings show that uPA may work via an independent pathway to angiogenesis and therefore combined blockade of uPA and angiogenesis may have additional therapeutic benefits. It also shows, as recently demonstrated in animal models, that PAI-1 may be a key regulator of vascular remodelling in human cancer.     

血管内皮细胞生长因子和血管生成与胃癌发展的关系

目的探讨血管内皮细胞生长因子（ＶＥＧＦ）和血管生成与胃癌发展的关系。方法应用免疫组织化学和原位分子杂交技术,检测５６例人胃癌组织ＶＥＧＦ蛋白表达和微血管密度（ＭＶＤ）及部分胃癌ＶＥＧＦｍＲＮＡ表达,分析ＶＥＧＦ和ＭＶＤ、及其与胃癌组织学分型、浸润深度、生长方式、淋巴结转移、远处转移和预后的关系。结果ＶＥＧＦ阳性者ＭＶＤ值显著高于阴性者（Ｐ＜００１）,ＶＥＧＦ表达和ＭＶＤ与胃癌浸润深度（Ｐ＜００１）、淋巴结转移（Ｐ＜００５）和远处转移（Ｐ＜０．０５）密切相关,而与组织学分型和生长方式无关（Ｐ＞００５）;ＶＥＧＦ表达阳性或ＭＶＤ≥４３的胃癌患者５年生存率较低;ＶＥＧＦｍＲＮＡ表达与ＶＥＧＦ蛋白表达具有一致性,但其分布不同。结论ＶＥＧＦ与胃癌的血管生成密切相关,对胃癌的生长和浸润转移有促进作用,ＶＥＧＦ和ＭＶＤ可作为反映胃癌生物学行为的指标之一     

Urokinase-type plasminogen activator receptor in gastric cancer: tissue expression and prognostic role

The urokinase-type plasminogen activator (UPA) and its inhibitor PAI-1 are thought to play an important part in gastric cancer (GC) invasion and metastasis. Little is known about the behavior and prognostic impact of the receptor for UPA (UPAR). The aims of the present study were: (1) to measure UPAR, UPA and PAI-1 levels in GC and in non-malignant tissue distant from the tumor (NORM); (2) to evaluate their relationship with histomorphological parameters; and (3) to determine their prognostic value. UPAR, UPA and PAI-1 levels were determined by ELISA in GC and NORM samples from 20 patients with GC undergoing surgery. The GC was also examined in terms of the presence (n=10) or absence (n=10) of metastasis, differentiation (five differentiated, 15 undifferentiated) and histotype. Survival was analysed using life table analysis. UPAR, UPA and PAI-1 were significantly higher in GC vs NORM, in the presence of metastasis (UPAR, UPA) and in undifferentiated GC (UPAR, PAI-1). UPAR significantly correlated with UPA and PAI-1. Low levels of UPAR (P=0.04), UPA (P=0.007) and PAI-1 (P=0.02) were associated with a better survival. Our results demonstrate a sharp increase in UPAR in GC and suggest a prognostic role for it. The concomitant activation of UPAR, UPA and PAI-1 in GC confirm the important role of the plasminogen activator system in the process of invasion and metastasis.     

Expression of angiopoietin 1, 2 and their common receptor Tie2 in human gastric carcinoma: implication for angiogenesis

Angiogenesis, formation of new microvessels providing oxygen and nutrient supply, is essential for tumor growth. It is dependent on the production of angiogenic growth factors by tumor cells. Angiopoietin 1 (Ang-1) and 2 (Ang-2) and their common receptor, Tie2, are thought to be critical regulators of tumor angiogenesis. We examined expression of Ang-1, Ang-2, and their common receptor Tie2 mRNAs and proteins in gastric cancers using in situ hybridization and immunohistochemistry. We also investigated the relationship between their expression and differentiation of cancer cells, lymph node metastasis, tumor size, depth of cancer cell invasion, TNM staging and microvessel density (MVD). The expression of Ang-1, Ang-2, and Tie2 mRNA in cancer cells significantly correlated with the MVD (p<0.001, <0.001 and =0.019, respectively). Ang-1 and Tie2 positivity correlated with advanced gastric cancers (p<0.05) and larger cancers had higher positive rates of Ang-1, Ang-2, and Tie2 mRNA expression (p<0.001, =0.010 and =0.039, respectively). Significant positive correlations were also found between mRNA expression of Tie2 and those of Ang-1 and Ang-2 (p<0.01 and <0.001, respectively). These findings indicate that the expression of Ang-1 and Ang-2 is important for tumor angiogenesis, and suggest a possible role of autocrine/paracrine function of angiopoietin/Tie2 system in gastric cancer progression.