Heterogeneity of Carcinoembryonic antigen expression in human colon cancer cell lines.

Abstract

Environmental causes of colon cancer have been difficult to elucidate. This is in large part due to the fact that no adequate marker for early neoplastic changes in colon tissue has been found. Carcinoembryonic antigen (CEA) is a glycoprotein that has shown promise in some clinical studies for the detection of colon cancer (Lawrence, 1975; Zamcheck, 1975). In order to study the relationship between CEA and malignancy, I chose to work with a continuously growing human colon cancer line, WiDr (Noguchi, 1975). The original WiDr line is quite heterogeneous in CEA expression, ranging from cells with little or no surface CEA to cells with large amounts of CEA. I have utilized the technology of flow cytometry to select a population of WiDr cells producing an increased amount of CEA. After sorting and growing the cells into bulk culture, the resulting population exhibited a substantial increase in the relative amount of CEA expression, however, expression was still heterogeneous. Correlated DNA-CEA cytograms showed that the increased CEA production was present in all parts of the cell cycle, and was not restricted to any particular phase. The enriched population was tested in nude mice to assess the possible role of CEA in tumorigenicity. Light microscope examination of histologic sections of tumors in nude mice exhibited increased immunoperoxidase localization of CEA in the sorted population. Thus, many of the discrepancies that have been found in the literature may be due to the marked heterogeneity of CEA expression seen in some colon cancers.