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.
