IMMUNOGLOBULIN A AND THE HUMAN GASTROINTESTINAL TRACT

根据我们以前的研究结果，我们假设某些 结肠上皮细胞上的表面抗原被极化，即，表示 选择性地在顶端或基底侧质膜上。 在 结肠癌，这种极性缺乏，正常的顶面 抗原在肿瘤细胞的表面上扩散表达。 这些异常表达的抗原，与那些 仅限于正常上皮细胞的顶端，暴露于 流通，因此，应该可以获得特定的攻击， 免疫抑制剂。 我们试图建立一种表达异常的动物模型， 结肠癌的表面抗原。 在小鼠中诱发结肠癌 大鼠给予二甲基肼（DMH）。 抗体 特异于正常成熟结肠上皮细胞的顶膜抗原 小鼠和大鼠的细胞被用来确定这些顶端是否 抗原在癌细胞上弥散表达。 发现该 癌细胞不表达我们的抗血清检测到的抗原。 这 结果表明，结肠癌缺乏分化抗原 通常存在于成熟的结肠上皮细胞上。 目前的工作将 进一步调查这种可能性。 我们将从不同阶段的细胞中制备质膜， 大鼠结肠隐窝中的分化。 蛋白质和糖蛋白 将分析膜的组分并与相应的 DMH诱导结肠癌细胞质膜的组分 细胞 这些数据将确定细胞在正常的隐窝， 结肠癌细胞的膜组成。 这种正常细胞 将被分离并用于制备异源抗体 顶膜抗原 然后用抗体来确定 未成熟结肠细胞上的正常极化抗原是否变得 在DMH诱导的原位癌上随机表达。 如果发生这种情况， 抗体将用于免疫治疗， 结肠癌。

Based on results of our previous research, we hypothesize that certain surface antigens on colonic epithelial cells are polarized, i.e., expressed selectively on either the apical or basolateral plasma membranes. In colonic carcinoma, this polarity is lacking, and normal apical surface antigens become expressed diffusely on surfaces of the neoplastic cells. These aberrantly expressed antigens, in contrast to those that are restricted to apices of normal epithelial cells, are exposed to the circulation and, hence, should be accessible to specific attack by immunotherapeutic agents. We have attempted to develop an animal model of aberrantly expressed surface antigens in colonic cancer. Colonic cancers were induced in mice and rats by the administration of dimethylhydrazine (DMH). Antibodies specific for apical membrane antigens of normal, mature colonic epithelial cells of the mouse and rat were used to determine whether these apical antigens are expressed diffusely on cancer cells. It was found that the cancer cells did not express antigens detected by our antisera. This outcome suggests that the colonic cancers lack differentiation antigens normally present on mature colonic epithelial cells. The present work will investigate that possibility further. We will prepare plasma membranes from cells at various stages of differentiation in rat colonic crypts. The protein and glycoprotein components of the membranes will be analyzed and compared to corresponding components of plasma membranes prepared from DMH-induced colonic cancer cells. These data will identify cells in the normal crypt that correspond in membrane composition to the colonic cancer cells. Such normal cells will be isolated and used for the preparation of heterologous antibodies to apical membrane antigens. The antibodies will then be used to determine whether the normally polarized antigens on immature colonic cells become randomly expressed on DMH-induced in situ cancers. If this occurs, the antibodies will be used in immunotherapy against transplanted and in situ colonic cancers.