Orntoft T F, Wolf H, Watkins W M
Department of Experimental Clinical Oncology, Aarhus County Hospital, Denmark.
Cancer Res. 1988 Aug 1;48(15):4427-33.
Immunohistochemistry has led to the finding of an expression of ABO-related blood group antigens in normal and malignant bladder urothelium which is different from that found on erythrocytes from the same individual. This includes a loss of blood group ABO expression in malignant urothelium, and the expression of Leb antigens in normal and malignant cells from individuals with Le(a+b-) and Le(a-b-) erythrocytes. To elucidate the mechanism of this blood group antigen expression in urothelium we have analyzed the activity of the specific glycosyltransferases encoded by the ABO, Se, H, Le, and X blood group genes in normal and malignant urothelium. Biopsies of normal urothelium were obtained from 22 individuals and biopsies of urothelial tumors from 20 individuals. The tissue donors were typed for ABO, Lewis, and secretor status on erythrocytes and saliva. The biopsies were disaggregated to single cell suspensions, and the activity of the individual glycosyltransferases was determined as pmol of labeled sugar incorporated by oligosaccharide acceptors per 100,000 cells. The A (alpha-3-N-acetyl-D-galactosaminyl) and B (alpha-3-D-galactosyl) gene-specified transferases showed no activity in malignant cells, whereas all other enzymes examined were expressed in both normal and malignant cells. Secretors and nonsecretors showed the same alpha-2-L-fucosyltransferase activity in both normal and malignant cells, whereas the alpha-3-L-fucosyltransferase was reduced (P less than 0.02) in malignant cells from Lewis positive individuals. The Lewis gene-encoded alpha-4-L-fucosyltransferase showed a similar activity in Lewis positive and negative individuals. These results indicate that the disappearance of A and B blood group antigens in bladder tumors and the expression of Leb antigens in normal and malignant cells from individuals with Le(a+b-) and Le(a-b-) erythrocytes are due to corresponding differences in glycosyltransferases. The results indicate that the ABO, H, Se, and Le genes are subjected to a tissue-dependent differential expression.
免疫组织化学已发现ABO相关血型抗原在正常和恶性膀胱尿路上皮中的表达，这与同一个体红细胞上的表达不同。这包括恶性尿路上皮中血型ABO表达的缺失，以及来自Le(a+b-)和Le(a-b-)红细胞个体的正常和恶性细胞中Leb抗原的表达。为了阐明尿路上皮中这种血型抗原表达的机制，我们分析了ABO、Se、H、Le和X血型基因编码的特定糖基转移酶在正常和恶性尿路上皮中的活性。从22名个体获取正常尿路上皮活检样本，从20名个体获取尿路上皮肿瘤活检样本。对组织供体的红细胞和唾液进行ABO、Lewis血型及分泌状态分型。将活检样本解离成单细胞悬液，通过每100,000个细胞中寡糖受体掺入的标记糖的皮摩尔数来测定各个糖基转移酶的活性。A（α-3-N-乙酰-D-半乳糖胺基）和B（α-3-D-半乳糖基）基因特异性转移酶在恶性细胞中无活性，而所检测的所有其他酶在正常和恶性细胞中均有表达。分泌型和非分泌型个体在正常和恶性细胞中均表现出相同的α-2-L-岩藻糖基转移酶活性，而Lewis阳性个体的恶性细胞中α-3-L-岩藻糖基转移酶活性降低（P<0.02）。Lewis基因编码的α-4-L-岩藻糖基转移酶在Lewis阳性和阴性个体中表现出相似的活性。这些结果表明，膀胱肿瘤中A和B血型抗原的消失以及来自Le(a+b-)和Le(a-b-)红细胞个体的正常和恶性细胞中Leb抗原的表达是由于糖基转移酶的相应差异所致。结果表明ABO、H、Se和Le基因存在组织依赖性差异表达。
