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

腺癌细胞中糖基转移酶的表达机制-以子宫内膜和卵巢腺癌为对象的研究-

• 批准号: 06454479
• 负责人: NOZAWA Shiro
• 金额: $ 4.48万
• 依托单位: Keio University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454479/
• 关键词: fucosyltransferase; galactosyltransferase; endometrial cancer; ovarian cancer

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

我们研究了聚焦碳水化合物链在子宫内膜癌中表达的机制和生物学意义。我们测量了来自子宫内膜癌的两种SNG-II亚型：SNG-S （Lewis^b型碳水化合物链表达亚株）和SNG-W （H型碳水化合物链表达亚株）的focusyltransferase （FT）活性。在α 1- 2f_1 - 3ft、α 1-4FT活性中，只有α 1-4FT活性在SNG-S组明显高于SNG-W组。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Lewis^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聚焦碳水化合物链的机制。在体外研究这些细胞与血管内皮的粘附时，SNG-W细胞的粘附数量约为SNG-S细胞的两倍。在裸鼠尾静脉注射两种亚株，观察其肺转移频率，发现SNG-W比SNG-S更容易发生肺转移。抗h型碳水化合物链抗体可剂量依赖性地抑制SNG-W对血管上皮的粘附，但其他血型相关碳水化合物链抗体不抑制SNG-W对血管上皮的粘附。SNG-W经抗h型碳水化合物链抗体处理后用于裸鼠肺转移模型，其转移频率低于未处理裸鼠。这些结果表明Lewis^b型和H型碳水化合物链的表达参与了子宫内膜癌细胞粘附血管上皮和转移等生物学特性。同时表明，表达H型碳水化合物链的子宫内膜癌细胞可能具有较高的转移率。与肿瘤相关的半乳糖转移酶（GalT）， GAT被认为是来源于健康个体的GalT的低聚物，在卵巢癌患者的血清中显著升高。为了阐明GAT在卵巢癌中特异性释放的原因，(1)将卵巢癌细胞系中GalT mRNA的表达与培养上清中GAT和总GalT的含量进行比较，(2)测定卵巢癌患者手术切除前后血清中GAT和总GalT的浓度。作为结果,(1)细胞系高尔特mRNA的表达是在协议的手枪或全部高尔特释放,和(2)得到的试验或总高尔特血清显示肿瘤切除导致得到的迅速减少,同时高尔特总额并未反映肿瘤状态,表明手枪被释放主要来自肿瘤细胞和血清的高尔特几个组织修改总高尔特的浓度。少

项目成果

久布白兼行: "子宮体癌におけるMSN-1認識抗原の組織接着,ならびに転移に与える影響" 日本産科婦人科学会雑誌. 47. 163-164 (1995)

Kaneyuki Kubushiro：“MSN-1识别抗原对子宫内膜癌组织粘附和转移的影响”日本妇产科学会杂志47。163-164（1995）。

高松 潔: "婦人科の腫瘍マーカー" 臨床検査. 39. 1273-1280 (1995)

高松清：《妇科肿瘤标志物临床检查》39。1273-1280（1995）。

Yoshihiro Akimoto, Daisuke Aoki, et al: "Immunocytochemical localization of the protein reactive to human beta 1,4-galactosyltransferase antibodies during chick embryonic skin differntiation." The Anatomical Record. 234. 109-119 (1995)

Yoshihiro Akimoto、Daisuke Aoki 等人：“在鸡胚胎皮肤分化过程中，对人 β 1,4-半乳糖基转移酶抗体具有反应性的蛋白质进行免疫细胞化学定位。”

Daisuke Aoki, et al: "Phenotypic alterations of a carbohydrate antigen, blood group A type 3 chain, in neoplastic tansformation of uterine cervix." Med.Electron Microscopy. 27 (3-4). 312-314 (1994)

Daisuke Aoki 等人：“碳水化合物抗原（A 型 3 型血型链）在子宫颈肿瘤转化中的表型改变。”

Daisuke Aoki, et al: "Phenotypic alteration of carbohydrate antigens in gynecological malignancy." Acta Histochem.Cytochem.28 (2). 197-201 (1995)

Daisuke Aoki 等人：“妇科恶性肿瘤中碳水化合物抗原的表型改变。”