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胃肠间质瘤组织中Hpa表达与螺旋CT征象的相关性研究
胃肠道间质瘤(gastrointestinal stromal tumor,GIST)是胃肠道除平滑肌肿瘤、神经鞘瘤及神经纤维瘤以外的间叶源性肿瘤.螺旋CT可以在较多征象上检测胃间质瘤的恶性程度,对临床早期诊断和治疗以及评价预后具有重要的指导价值;乙酰肝素酶(heparanase,Hpa)在肿瘤细胞侵袭中起着极其重要的作用,与肿瘤转移之间的关系也日益受到关注,有关Hpa与肿瘤关系报道较多,但在GIST中报道尚少见.
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heparanase基因及其蛋白表达产物在肿瘤扩散与转移中的作用
阻止肿瘤细胞扩散与转移的主要屏障是细胞外基质(extracellular matrix, ECM)和基底膜(basement menbrane,BM),ECM和BM主要由结构蛋白和糖胺聚糖两种成分构成.糖胺聚糖的主要成分是硫酸乙酰肝素蛋白多糖(heparan sulfate proteoglyean,HSPG),heparanase基因在易发生扩散与转移的肿瘤细胞表达上调且表达的产物能降解HSPG,从而促进肿瘤细胞的扩散与转移.文中着重阐述heparanase基因及其蛋白表达产物调节与在肿瘤扩散与转移中的作用现状及相关研究进展.
关键词： heparanase 肿瘤 转移 侵袭性 -
heparanase通过调控EMT促进人膀胱移行细胞癌细胞T24迁移及侵袭的作用研究
目的 探讨乙酰肝素酶(heparanase)是否通过上皮-间充质转化(EMT)影响膀胱移行细胞癌细胞的侵袭及迁移能力.方法 利用荧光定量PCR来检测人膀胱移行细胞癌细胞T24、EJ、MGH-U1以及BIU-87中heparanase的表达水平;设计并合成靶向heparanase的特异性shRNA,通过脂质体转染法转染heparanase表达高的膀胱移行细胞癌细胞T24以构建稳定低表达heparanase细胞株,通过Western blot法检测和定量PCR来验证shRNA的干扰效率;通过transwell法检测干扰后细胞的迁移及侵袭能力,Western blot法检测EMT相关指标E-cadherin和N-cadherin以及其上游信号分子Snail和WNT-5a的变化.结果 heparanase-shRNA转染后,能够有效抑制T24细胞中heparanase的表达;Transwell法结果显示,heparanase干扰组细胞侵袭及迁移能力显著低于阴性对照组(P ＜0.001).Western blot法检测结果发现,heparanase干扰组细胞的E-cadherin表达增加,N-cadherin的表达降低;此外,heparanase干扰组细胞的Snail以及WNT-5a表达较对照组显著下降.结论 运用RNA干扰技术能够有效沉默T24细胞的heparanase基因,并诱导其迁移侵袭能力的下降,其可能的机制是通过调节EMT的上游信号分子Snail、WNT-5a的表达来调控EMT,从而影响膀胱移行细胞癌细胞的迁移及侵袭.提示heparanases可能在膀胱移行癌T24细胞的发生发展中起重要作用,抑制heparanase的表达可能成为一种治疗膀胱移行细胞癌的新方法.
关键词： heparanase 上皮-间充质转化 膀胱移行细胞癌 -
Heparanase与bFGF在膀胱移行细胞癌中的表达研究
目的 探讨类肝素酶(heparanase,Hpa)与碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)在膀胱移行细胞癌(transitional cell carcinoma of the bladder,TCCB)发生、发展中的作用及意义.方法 应用免疫组织化学 S-P法,检测69例BTCC和9例正常膀胱组织中Hpa和bFGF的表达.结果 膀胱癌中,Hpa阳性表达率为42.03%;bFGF阳性表达率为44.93%;Hpa与bFGF共表达阳性率为31.89%;9例正常膀胱黏膜中均未见Hpa和bFGF阳性表达.Hpa与bFGF表达均随着膀胱癌病理分级和临床分期的升高而增强(P＜0.05).结论 Hpa与bFGF可能作为预测膀胱移行细胞癌进展的指标及肿瘤治疗靶点,并有可能成为一个有效的预后指标.
关键词： heparanase 膀胱肿瘤 血管形成 碱性成纤维细胞生长因子 -
Heparanase Expression Correlates with Angiogenesis and Lymphangiogenesis in Human Lung Cancer
Background and objective Heparanase has been thought to be a good molecular marker of tumor, and the heparanase expression level was correlated closely with tumor metastasis. In this study, we investigate the effects of heparanase on angiogenesis and lymphangiogenesis of lung cancer and the relationship between heparanase expression and vascular endothelial growth factor (VEGF), vascular endothelial growth factor-C (VEGF-C).Methods Immunohistochemistry was used to detect the expression of heparanase, VEGF, VEGF-C protein and microvascular density (MVD), lymphatic vessel density (LVD) in 115 cases of non-small cell lung cancer (NSCLC) and 45 cases of adjacent normal tissue samples.Results Our results showed that heparanase expression was significantly increased in 91 (79.13%) of the 115 cases and correlated with lymph node metastasis (node positive rate 87.0%; node negative rate 36.8%; P=0.003). Heparanase positive expression cases have significantly higher concentration of microvascular density (MVD) and lymphatic vessd density (LVD) as compared with heparanase negative expression cases (P<0.01, P<0.01, respectively), heparanase expression was significantly correlated with VEGF, VEGF-C expression in NSCLC.Conclusion Heparanase overexpression was associated with angiogenesis and lymphangiogenesis of lung cancer, targeting ofheparanase may represent a significant therapeutic potential for lung cancer.
