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是一种特异性的胚胎抗原-4（SSEA-4或MSGB5）合成酶，将唾液酸转移至GB5。在8个肾细胞癌细胞系中的7个中，ST3GAL II mRNA的水平升高，并使用北机器人分析检查了所有6种肾细胞癌组织。我们进一步测试，发现使用定量PCR的27例肾细胞癌病例中，ST3GAL II的水平升高。从这些研究中可以表明，ST3GAL II与肾脏的致癌作用有关。使用ACHN细胞系，通过siRNA抑制SIRNA的ST3GAL II mRNA表达为30％。 siRNA也提高了MSGB5的表达。与抑制ST3GAL II，ACHN细胞的增殖和侵袭的伴随。我们最近发现了一种新型的疾病，RM2抗原（β1，4-GALNAC-DISIALLYL-LC4），来自肾细胞癌。我们检查了RM2抗原在114例肾细胞CA…更多的Rcinoma病例的新鲜切片中的表达。 RM2抗原在15例（13％）中为阳性，其中9例在初始诊断时已经有转移，随访期间有2例发生转移。由于在RM2抗原阳性病例的73％（11/15）中检测到转移，因此RM2抗原可能与肾细胞癌的恶性潜力有关。 RM2抗原是由I型链条链和神经节系列结构组成的独特寡糖。乳酸系列结构广泛分布在上皮细胞中，而神经节抗原在神经皮质起源的细胞中很普遍。另一方面，虽然前列腺癌会形成上皮并表达上皮特征，例如前列腺酸性磷酸酶和PSA，但神经内分泌分化是前列腺癌的特征。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。这，我们检查了75例自由基细胞切除术标本中RM2抗原的表达。在格里森模式3和[大于或等于] 4之间观察到了RM2表达水平的明显差异。较高的RM2抗原表达与原发性Gleason Pattern 4，高格里森评分，较大的肿瘤体积和晚期肿瘤阶段显着相关。此外，在较高表达组中，无PSA失败的5年无生存率显着降低。我们对乙烯基转移酶和寡糖的研究表明，通过恢复诸如糖基质酶的糖基化酶水平，具有糖链作为一般现象的质量或定量变化的癌症的可能性。较少的