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

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，负责将唾液酸转移到GB5。Northern BOT分析显示，8株肾癌细胞株中有7株ST3Gal II基因表达上调，6例肾癌组织中ST3Gal II基因表达水平全部升高。我们进一步检测发现，在27例肾细胞癌中，ST3Gal II的表达水平在定量聚合酶链式反应中多数升高。这些研究表明，ST3Gal II与肾癌的发生有关。在ACHN细胞中，siRNA对ST3Gal II基因表达的抑制作用是无序(Mock)siRNA的30%。SiRNA还能降低MSGb5的表达。在抑制ST3GalII的同时，β细胞的增殖和侵袭能力也下降。我们最近从肾癌中发现了一种新的二唾液酸神经节苷脂RM2抗原(ST3Gal1，4-GalNAc-disialyl-Lc4)。我们检测了114例肾细胞癌…新鲜冰冻切片中RM2抗原的表达。更多的肺癌。RM2抗原阳性15例(13%)，其中9例初诊时已有转移，2例在随访期发生转移。由于RM2抗原阳性患者中有73%(11/15)有转移，RM2抗原可能与肾癌的恶性潜能有关。RM2抗原是一种独特的寡糖，由乳糖系列、I型链和神经节系列结构组成。乳胶系列结构广泛分布于上皮细胞，而神经节系列抗原普遍存在于神经外胚层来源的细胞中。另一方面，前列腺癌从上皮细胞发展而来，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两面性。因此，我们检测了75例前列腺癌根治术标本中RM2抗原的表达。RM2抗原表达与Gleason 4型、Gleason评分高、肿瘤体积大、分期分期有关。我们对唾液酸转移酶和寡糖的研究表明，通过将唾液酸基转移酶等糖基转移酶的水平恢复到正常水平，可以治疗糖链发生质或量变化的癌症。较少

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