Maturation-induction of tumor cells using a human colon carcinoma model

The establishment of a maturation-induction model using human colon cancer cells as targets is reported. Two colon carcinoma cell lines were established from human tumors; one line was heterogeneous and was cloned into two distant subpopulations. Cells from these lines and clones and cells from an established human colon carcinoma cell line were treated in vitro with N,N-dimethylformamide (DMF) and were compared to untreated cells according to two general sets of criteria. One set contains characteristics that define a cell as transformed (i.e., anchorage independence and tumorigenicity for nude mice), and the second set contains three antigenic marker systems that would provide evidence that maturation is occurring in treated human colon cancer cells. These colon tissue-or tumor-related markers include carcinoembryonic antigen (CEA), colonic mucoprotein antigen (CMA), and the human blood group determinants. DMF-treated cells are less malignant than untreated cells; the treated cells show a marked reduction in tumorigenicity and in clonogenicity in soft agar. Each of the markers indicates that the treated cells are better differentiated than their untreated counterparts. For example, treated cells show increased expression of normal-CMA and decreased expression of tumor-CMA compared to untreated cells. Cells removed from DMF reverted to express the tumorigenicity, growth properties, and antigens characteristic of their untreated counterparts. Therefore, DMF reversibly induces in cultured colon cancer cells a less malignant phenotype with concomitant maturational effects. These results indicate that this model is appropriate for study of maturation-induction in human colon tumor cells, and has potential application to other types of human carcinomas.