Carcinoembryonic Antigen Has a Different Molecular Weight in Normal Colon and in Cancer Cells due to W-Glycosylation Differences'

Carcinoembryonic antigen, an apical membrane glycoprotein expressed in normal human colonie epithelial cells, colonie polyps, tumor, and tissue culture cell lines originating from colonie adenocarcinomas, is generally considered to have a molecular weight of 180,000. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis associated with immunoprecipitation or immunoblotting with both monoclonal (Mab 517 and Mah 601) and poh donai antibodies, we observed that carcinoembryonic anti gen was actually expressed as two discrete apparent molecular weight forms in normal tissues: a broad band averaging at M, 200,000 and a sharp band at M, 130,000. This constituted the phenotype of the normal colon. In cancer cells we detected a single band at M, 170,000 or lower. This variation was mainly the consequence of a modification of the glycosylation pattern of the molecule since deglycosylation by ¿V-glycanase or biosynthesis in the presence of tunicamycin always produced a single molecular weight form, whether or not the source of tissue was normal or cancerous. By close inspection of benign, moderately transformed, and carcinomatous human colonie polyps we noticed that this shift in the molecular weight of carcinoembryonic antigen preceded the detection of other cancer markers such as nonspecific cross-reacting antigen at M, 95,000 or the histolÃ3gica! modifications leading to malignant diagnosis. Carcinoem bryonic antigen constitutes, therefore, an important model with which to study the modifications of the glycosylation pattern induced during cancer biogenesis.