Siddiki B, Ho J J, Huang J, Byrd J C, Lau E, Yuan M, Kim Y S
Gastrointestinal Research Laboratory, Veterans Affairs Medical Center, San Francisco, CA 94121.
Int J Cancer. 1993 May 28;54(3):467-74. doi: 10.1002/ijc.2910540319.
Exposure of core carbohydrate structures such as NeuAc alpha2-6GalNAc-Ser/Thr (sialosyl-Tn) in mucus glycoproteins is often associated with malignant transformation in a number of different tissues. Reagents that specifically identify such structures would be useful in the diagnosis of cancer. Monoclonal antibody JT10e has been produced against mucins from xenografts of LS174T colon cancer cells but also reacts with mucins of pancreatic cancer xenografts. The following data suggest that JT10e reacts with sialosyl-Tn: (I) reactivity with bovine and ovine submaxillary mucins; (2) reactivity sensitive to neuraminidase or mild acid; (3) inhibition of reactivity by NeuAc and NeuAc alpha2-6 lactose; and (4) lack of reactivity with other glycoproteins with related carbohydrate structures but no sialosyl-Tn. JT10e is distinguishable from 2 other antibodies which react with sialosyl-Tn, B72.3 and TKH2 because JT10e: (a) did not react with normal gastric tissue while B72.3 and TKH2 did; (b) was only partially inhibited by TKH2 and not at all by B72.3; (c) did not react with Tn antigen while B72.3 did; and (d) bound more strongly to pancreatic cancer mucins than did either B72.3 or TKH2. JT10e reacted with a high percentage of malignant colonic, pancreatic, gastric and mammary tissues but not with the corresponding normal tissues. A high percentage of patients with colonic, pancreatic, gastric, mammary and lung cancers had elevated blood levels of JT10e antigen. A number of colonic cancer patients had elevated JT10e antigen levels without corresponding elevations in CA19-9 levels. These results suggest that JT10e antibody could be used in conjunction with other mucin markers to improve the identification of malignancy in colon, and to study the structure of oligosaccharides in cancer mucins.
黏液糖蛋白中核心碳水化合物结构如NeuAcα2-6GalNAc-Ser/Thr（唾液酸化Tn）的暴露常与多种不同组织的恶性转化相关。特异性识别此类结构的试剂在癌症诊断中会很有用。单克隆抗体JT10e是针对LS174T结肠癌细胞异种移植物中的黏蛋白产生的，但也与胰腺癌异种移植物的黏蛋白发生反应。以下数据表明JT10e与唾液酸化Tn发生反应：（I）与牛和羊的下颌下黏蛋白有反应性；（2）对神经氨酸酶或弱酸敏感的反应性；（3）NeuAc和NeuAcα2-6乳糖对反应性的抑制作用；以及（4）与具有相关碳水化合物结构但无唾液酸化Tn的其他糖蛋白无反应性。JT10e与另外两种与唾液酸化Tn反应的抗体B72.3和TKH2不同，因为JT10e：（a）不与正常胃组织反应，而B72.3和TKH2会反应；（b）仅被TKH2部分抑制，完全不被B72.3抑制；（c）不与Tn抗原反应，而B72.3会反应；并且（d）与胰腺癌黏蛋白的结合比B72.3或TKH2更强。JT10e与高比例的恶性结肠、胰腺、胃和乳腺组织发生反应，但不与相应的正常组织反应。高比例的结肠癌、胰腺癌、胃癌、乳腺癌和肺癌患者血液中JT10e抗原水平升高。一些结肠癌患者JT10e抗原水平升高，而CA19-9水平无相应升高。这些结果表明，JT10e抗体可与其他黏蛋白标志物联合使用，以改善结肠癌恶性肿瘤的识别，并研究癌性黏蛋白中寡糖的结构。
