Sugiyama T, Brown W R, Ahnen D J
Department of Medicine, Denver Veterans Administration Medical Center, Colorado.
Gastroenterology. 1988 Feb;94(2):331-42. doi: 10.1016/0016-5085(88)90420-9.
Previously, we reported that two glycoproteins, carcinoembryonic antigen and secretory component, are preferentially expressed on the apical or laterobasal surfaces, respectively, of normal human colonic epithelial cells, whereas these antigens may be expressed over the entire cell surface of colonic cancer cells. These observations have prompted us to develop an animal model of aberrantly distributed normal surface antigens in colonic carcinoma. We prepared four monoclonal antibodies, three of which react specifically with antigens located on the microvillus surface and one that reacts specifically with the laterobasal surface of normal rat colonocytes. Three of the four cell-surface antigens were expressed by cells at all levels of the colonic crypt, but one of the microvillar antigens (p66) was expressed only on the mature colonocytes at the luminal surface. We then documented that a microvillus antigen (p66) detected by one of the antibodies and a laterobasal membrane antigen detected by another antibody were expressed over the entire surface of poorly differentiated colonic carcinoma cells induced by dimethylhydrazine. p66 was more often expressed on poorly differentiated colonic cancers than were the other three antigens. These observations indicate that (a) polarity of surface membrane antigens is a characteristic of normal rat colonic epithelial cells, (b) this polarity is not present in some experimental colonic carcinomas, and (c) the malignant phenotype of colonic carcinoma cells does not result merely from a block in normal differentiation of colonocytes.
此前，我们报道过两种糖蛋白，即癌胚抗原和分泌成分，分别优先表达于正常人结肠上皮细胞的顶端或侧基底面，而这些抗原可能在结肠癌细胞的整个细胞表面表达。这些观察结果促使我们建立一种结肠癌中正常表面抗原异常分布的动物模型。我们制备了四种单克隆抗体，其中三种特异性识别位于微绒毛表面的抗原，一种特异性识别正常大鼠结肠细胞的侧基底面。四种细胞表面抗原中的三种在结肠隐窝各水平的细胞中均有表达，但其中一种微绒毛抗原（p66）仅在管腔表面的成熟结肠细胞上表达。然后我们记录到，由一种抗体检测到的微绒毛抗原（p66）和由另一种抗体检测到的侧基膜抗原在二甲基肼诱导的低分化结肠癌细胞的整个表面均有表达。与其他三种抗原相比，p66在低分化结肠癌中更常表达。这些观察结果表明：（a）表面膜抗原的极性是正常大鼠结肠上皮细胞的一个特征；（b）这种极性在一些实验性结肠癌中不存在；（c）结肠癌细胞的恶性表型不仅仅是结肠细胞正常分化受阻的结果。
