Xing P X, Lees C, Lodding J, Prenzoska J, Poulos G, Sandrin M, Gendler S, McKenzie I F
Austin Research Institute, Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australia.
Int J Cancer. 1998 Jun 10;76(6):875-83. doi: 10.1002/(sici)1097-0215(19980610)76:6<875::aid-ijc18>3.0.co;2-1.
Mucins are highly expressed in many different human cancers and numerous murine monoclonal antibodies (MAbs) to human mucins, particularly Mucin 1 (MUC1), have been produced. However, no such antibodies to murine mucin 1 (muc1) have been described and we now describe 6 different antibodies produced to murine muc1 and to human MUC1 cytoplasmic tail, either by immunising rats, or muc1 o/o mice with synthetic peptides or a fusion protein composed of glutathione-s-transferase (GST) linked to the tandem repeat region of muc1. The antibodies to both the extracellular tandem repeat region and to the cytoplasmic tail were found to react with mucin-containing murine tissues such as breast, stomach, colon, ovary, kidney and pancreas, and the staining patterns were similar to those found in humans. The reagents reacted specifically with muc1 peptides and tissues; however, some cross reactivity with other mucin-derived peptides was noted, particularly those containing the amino acid sequence TSS. Three different epitopes (TSS, TAVLSGTS and LSGTSSP) of the M30, M70 and MFP25 MAbs were detected. Of interest was the finding that some of the antibodies reacted with murine lymphocytes; it was not clear whether these reactions were due to mucin 1 on mouse lymphocytes (MUC1 was considered to be absent from human lymphocyte), or due to cross reaction with a sialic adhesion molecule on lymphocytes. The antibodies should prove valuable reagents when studying differentiation and expression in murine glandular tissues and the ontogeny of mucin-secreting tumours.
粘蛋白在许多不同的人类癌症中高度表达,并且已经产生了许多针对人类粘蛋白的鼠单克隆抗体(MAb),尤其是针对粘蛋白1(MUC1)的抗体。然而,尚未描述针对鼠粘蛋白1(muc1)的此类抗体,我们现在描述通过用合成肽或由与muc1串联重复区域连接的谷胱甘肽 - S - 转移酶(GST)组成的融合蛋白免疫大鼠或muc1基因敲除小鼠而产生的6种不同抗体,这些抗体针对鼠muc1和人类MUC1细胞质尾巴。发现针对细胞外串联重复区域和细胞质尾巴的抗体与含粘蛋白的鼠组织如乳腺、胃、结肠、卵巢、肾脏和胰腺发生反应,并且染色模式与在人类中发现的相似。这些试剂与muc1肽和组织特异性反应;然而,注意到与其他粘蛋白衍生肽有一些交叉反应,特别是那些含有氨基酸序列TSS的肽。检测到M30、M70和MFP25单克隆抗体的三个不同表位(TSS、TAVLSGTS和LSGTSSP)。有趣的是发现一些抗体与鼠淋巴细胞发生反应;尚不清楚这些反应是由于小鼠淋巴细胞上的粘蛋白1(人类淋巴细胞被认为不存在MUC1),还是由于与淋巴细胞上的唾液酸粘附分子发生交叉反应。在研究鼠腺组织中的分化和表达以及粘蛋白分泌肿瘤的个体发生时,这些抗体应被证明是有价值的试剂。