权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The roles of sialyltransferases involved in malignant progression of renal cell carcinoma

唾液酸转移酶在肾细胞癌恶性进展中的作用

基本信息

批准号：
15390483
负责人：
SAITO Seiichi
金额：
$ 7.04万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390483/
关键词：
Silayltransferase renal cell carcinoma RM2 antigen prostate cancer 腎細胞癌 sialyltransferase SSEA-4 ST3 Gal II siRNA ACHN stage-specific embryonic antigen-4 ST3Gal II 精巣腫瘍

项目摘要

We have found that ST3Gal II is a stage-specific embryonic antigen-4 (SSEA-4 or MSGb5) synthase, which transfers sialic acid to Gb5. Levels of ST3Gal II mRNA were increased in 7 out of 8 renal cell carcinoma cell lines and all 6 renal cell carcinoma tissues examined using Northern bot analysis. We further tested and found that levels of ST3Gal II were increased in most of 27 cases of renal cell carcinoma using quantitative PCR. From these studies it was indicated that ST3Gal II is associated with carcinogenesis of kidney. Inhibition of ST3Gal II mRNA expression by siRNA was 30% of that by disordered (mock) siRNA using ACHN cell line. Expression of MSGb5 was also decreased by siRNA. Concomitant with suppression of ST3Gal II, proliferation and invasion of ACHN cells were also decreased.We recently found a novel disialoganglioside, RM2 antigen (β1, 4-GalNAc-disialyl-Lc4) from renal cell carcinoma. We examined expression of RM2 antigen in fresh-frozen sections of 114 cases of renal cell ca … More rcinoma. RM2 antigen was positive in 15 cases (13%), out of which 9 had metastasis already at initial diagnosis and 2 developed metastasis during follow-up period. Since metastasis was detected in 73% (11/15) of RM2 antigen-positive cases, RM2 antigen may have relevance to malignant potential of renal cell carcinoma. RM2 antigen is a unique oligosaccharide composed of lacto-series type I chain and ganglio-series structure. Lacto-series structures were widely distributed in epithelial cells, whereas ganglio-series antigens were prevalent in cells of neuroectodermal origin. On the other hand, whereas prostate cancer develops form epithelium and expresses epithelial characteristics such as prostatic acid phosphatase and PSA, neuroendocrine differentiation is a feature of prostate cancer. Based on these facts, structural characteristics of RM2 antigen may reflect the dual nature of prostate cancer. Thus, we examined expression of RM2 antigen in 75 cases of radical prostatectomy specimens. A clear difference of RM2 expression level was observed between Gleason patterns 3 and 【greater than or equal】4. Higher expression of RM2 antigen was significantly associated with primary Gleason pattern 4, high Gleason score, larger tumor volume and advanced tumor stage. Furthermore, 5-year PSA failure free survival was significantly lower in the higher expression group.Our study on sialyltransferase and oligosaccharide showed the possibility of treating cancer, which has qualitative or quantitative changes of sugar chain as a general phenomenon, by restoring the level of glycosyltransferase such as sialyltransferase to normal. Less

我们发现ST3Gal II是一种阶段特异性的胚胎抗原-4 （SSEA-4或MSGb5）合成酶，它将唾液酸转移到Gb5。通过Northern bot分析，8种肾细胞癌细胞系中有7种和6种肾细胞癌组织中ST3Gal II mRNA水平升高。我们进一步检测发现，在27例肾细胞癌中，大多数ST3Gal II水平升高。这些研究表明ST3Gal II与肾脏癌变有关。在ACHN细胞系中，siRNA对ST3Gal II mRNA表达的抑制作用是无序（模拟）siRNA的30%。siRNA也降低了MSGb5的表达。抑制ST3Gal II的同时，ACHN细胞的增殖和侵袭也减少。我们最近从肾细胞癌中发现了一种新的二氮化脂苷，RM2抗原（β 1,4 - galnac -二氮化脂- lc4）。我们在114例肾细胞癌的冷冻切片中检测了RM2抗原的表达。RM2抗原阳性15例（13%），其中9例初诊已发生转移，2例随访期间发生转移。由于在73%（11/15）的RM2抗原阳性病例中检测到转移，因此RM2抗原可能与肾细胞癌的恶性潜能有关。RM2抗原是一种独特的低聚糖，由乳链I型链和神经节链结构组成。乳系列抗原在上皮细胞中广泛分布，而神经节系列抗原在神经外胚层细胞中普遍存在。另一方面，前列腺癌从上皮细胞发展并表达前列腺酸性磷酸酶和PSA等上皮特征，而神经内分泌分化是前列腺癌的一个特征。基于这些事实，RM2抗原的结构特征可能反映了前列腺癌的双重性质。因此，我们检测了75例根治性前列腺切除术标本中RM2抗原的表达。在Gleason模式3和【大于等于】模式4之间，RM2表达水平有明显差异。RM2抗原高表达与原发性Gleason模式4、Gleason评分高、肿瘤体积大、肿瘤分期晚期显著相关。此外，高表达组的5年PSA无失败生存率显著降低。我们对唾液基转移酶和寡糖的研究表明，通过恢复唾液基转移酶等糖基转移酶的正常水平，有可能治疗糖链发生定性或定量变化的癌症。少