Augmentation of carcinoembryonic antigen release from intact, viable tumor cells by a factor in human serum

Abstract

Measurement of carcinoembryonic antigen (CEA) levels in human serum is frequently used to detect tumor recurrence in patients with resected primary colorectal cancers. These levels are highly variable from patient to patient, and the mechanism that determines these levels is still poorly understood. Using a 6-h in vitro CEA-release assay, we determined that a factor in human and fetal bovine sera significantly augments the release of CEA from the tumor cell surface into cell culture supernatants. As little as 1% serum admixed with tumor cells results in CEA release up to 200% greater than that of serum-free controls. It is not inhibited by 1,10-phenanthroline or heat inactivation (of serum) but is calcium dependent. The electrophoretic mobility and membrane linkage of CEA released by serum appear to be identical to those of CEA released by bacterial phospholipase C. Because bacterial phospholipase C is known specifically to cleave the phosphoinositol (PI) glycan moiety that anchors CEA to the tumor cell surface, a mechanism of action for serum cleaving this anchor is suggested. The large range of CEA levels observed in patients with colorectal cancers may be related to differential sensitivity of the CEA membrane anchor to the CEA-releasing factor in serum.