The expression mechanism of glycosyltransferases in adenocarcimoma cells -a study using endometrial and ovarian adenocarcimomas-

我们研究了岩藻糖基化糖链在子宫内膜癌中的表达及其生物学意义。我们测定了子宫内膜癌来源的SNG-Ⅱ的两个亚株：SNG-S（一个刘易斯^B型糖链表达亚株）和SNG-W（一个H型糖链表达亚株）的岩藻糖基转移酶（FT）活性。在α 1- 2FT、α 1-3FT、α 1-4FT活性中，只有后者在SNG-S中明显高于SNG-W。这表明编码α 1-4FT的FTIII基因在SNG-S中的表达强于SNG-W。为了阐明刘易斯^B型和H型抗原的生物学意义，我们研究了SNG-S和SNG-W的细胞生物学特性，它们具有不同的表达岩藻糖基化碳水化合物链的机制。当在体外研究这些细胞与血管内皮的粘附时，粘附的SNG-W细胞的数量约为SNG-S细胞的两倍。当我在体内 ...更多信息 通过将两种亚株分别注入裸鼠尾静脉，观察肺转移率，结果表明SNG-W的肺转移率明显高于SNG-S。SNG-W与血管上皮的粘附作用可被抗H型糖链抗体抑制，呈剂量依赖性，但不被抗其它血型相关糖链抗体抑制。当SNG-W用抗H型糖链抗体处理并用于裸鼠肺转移模型时，转移频率低于未处理的动物。这些结果表明，刘易斯、B和H型糖链的表达与子宫内膜癌细胞的生物学特性如与血管上皮的粘附和转移有关。卵巢癌患者血清中与肿瘤相关的半乳糖基转移酶（GalT）（GAT）水平明显升高，GAT被认为是正常人GalT的寡聚体。为了阐明GAT仅从卵巢癌释放的原因，（1）将卵巢癌细胞系中GalT mRNA的表达与培养上清液中GAT和总GalT的量进行比较，和（2）在手术切除之前和之后测定卵巢癌患者血清中GAT和总GalT的浓度。结果表明：（1）细胞系中GalT mRNA的表达与GAT或总GalT的释放量相一致;（2）血清中GAT或总GalT的测定表明肿瘤切除后GAT迅速下降，而总GalT的量不能反映肿瘤的状态，这表明GAT主要从肿瘤细胞释放，并且在血清中，来自几种组织的GalT改变了总GalT的浓度。少

We studied the mechanism and biological significance of fucosylated carbohydrate chains expressed in endometrial cancer. We measured fucosyltransferase (FT) activity in two substrains of SNG-II derived from uterine endometrial cancer : SNG-S (a Lewis^b type carbohydrate chain expressing substrain) and SNG-W (an H type carbohydrate chain expressing substrain). Among alpha 1-2FTalpha 1-3FT,alpha 1-4FT activity, only the last was clearly higher in SNG-S than in SNG-W.This indicated that expression of the FTIII gene, which codes for alpha 1-4FT,was stronger in SNG-S than in SNG-W.In order to elucidate the biological significance of Lewis^b type and H type antigen, we studied the cell biological properties of both SNG-S and SNG-W,which have different mechanisms for expressing fucosylated carbohydrate chains as indicated above. When adhesion of these cells to the vascular endothelium was studied in vitro, the number of adherent SNG-W cells was about twice that of SNG-S cells. When in vivo me … More tastasis was studied by injecting the two substrains into the tail veins of nude mice and examining the frequency of lung metastasis, SNG-W showed significantly more lung metastasis than SNG-S.Adhesion of SNG-W to the vascular epithelium was dose-dependently inhibited by and anti-H type carbohydrate chain antibody, but was not inhibited byantibodies fro other blood-group related carbohydrate chains. When SNG-W was treated with the anti-H type carbohydrate chain anitibody and used in the nude mouse lung metastasis model, the frequency of metastasis was lower than in untreated animals. These results indicated that expression of the Lewis^b type and H type carbohydrate chains was involved in biological properties such as adhesion to the vascular epithelium and metastasis of uterine endometrial cancer cells. It was alsosuggested thet uterine endometrial cancer cells which express the H type carbohydrate chain may show a high rate of metastasis.Galactosyltransferase (GalT) associated with tumor, GAT,which is thought to be the oligomers of GalT derived from healthy individuals, is considerably elevated in sera of ovarian cancer patients. To elucidate why GAT is exclusively released from ovarian cancers, (1) the expression of GalT mRNA in ovarian cancer cell lines was compared with the amount of GAT and total GalT in culture supernatant and (2) the concentration of GAT and total GalT in sera from the ovarian cancer patients was determined before and after the surgical resection. As the result, (1) the expression of GalT mRNA in cell lines was in agreement with the amount of GAT or total GalT released, and (2) the assay of GAT or total GalT in the sera showed that the tumor resection resulted in the rapid decrease of GAT,meantime the amount of total GalT did not reflect the tumor status, suggesting that GAT were released mainly from the tumor cells and in the serum the GalT from several tissues modified the concentration of the total GalT. Less