Huang J, Byrd J C, Siddiki B, Yuan M, Lau E, Kim Y S
Gastrointestinal Research Laboratory, VA Medical Center, San Francisco, CA 94121.
Dis Markers. 1992 Mar-Apr;10(2):81-94.
In order to develop reagents that can detect the exposed core carbohydrate antigens of mucins, we have prepared monoclonal antibodies against partially deglycosylated LS174T human colon cancer mucin. The three monoclonal antibodies, 10F4, 15D3a, and 91S8, stained cancers of the colon, pancreas, stomach, breast, prostate, and lung to a greater extent than corresponding normal tissues. There was no staining of normal pancreas or breast, suggesting that these antibodies may be particularly useful for detecting cancers in these two organs. In homogenates of cultured cancer cells, antigen was detectable in three colon cancer cell lines, but not in a variety of other epithelial cancers. The epitope specificity of all three monoclonal antibodies appears to be for Tn antigen, i.e. GalNAc-alpha-Ser/Thr, based on their recognition of alpha-linked GalNAc, but not T antigen, sialyl Tn, or a range of other structures. However, the three anti-Tn antibodies differed in tissue staining specificity and in relative binding to different mucins. These monoclonal antibodies, prepared against deglycosylated colon cancer mucin, appear to be useful reagents for the immunohistochemical detection of epithelial cancers, especially pancreatic cancer and breast cancer.
为了开发能够检测黏蛋白暴露的核心碳水化合物抗原的试剂,我们制备了针对部分去糖基化的LS174T人结肠癌黏蛋白的单克隆抗体。三种单克隆抗体10F4、15D3a和91S8对结肠癌、胰腺癌、胃癌、乳腺癌、前列腺癌和肺癌的染色程度比对相应正常组织的染色程度更高。正常胰腺或乳腺未出现染色,这表明这些抗体可能对检测这两个器官中的癌症特别有用。在培养的癌细胞匀浆中,在三种结肠癌细胞系中可检测到抗原,但在多种其他上皮癌中未检测到。基于它们对α连接的GalNAc的识别,所有三种单克隆抗体的表位特异性似乎针对Tn抗原,即GalNAc-α-Ser/Thr,而不是T抗原、唾液酸化Tn或一系列其他结构。然而,这三种抗Tn抗体在组织染色特异性以及与不同黏蛋白的相对结合方面存在差异。这些针对去糖基化结肠癌黏蛋白制备的单克隆抗体似乎是用于上皮癌免疫组织化学检测的有用试剂,尤其是胰腺癌和乳腺癌。