AUGMENTATION OF CARCINOEMBRYONIC ANTIGEN RELEASE FROM INTACT, VIABLE TUMOR-CELLS BY A FACTOR IN HUMAN SERUM

Background: Measurement of carcinoembryonic antigen (CEA) levels in hu man serum is frequently used to detect tumor recurrence in patients wi th resected primary colorectal cancers. These levels are highly variab le from patient to patient, and the mechanism that determines these le vels is still poorly understood.Methods: Using a 6-h in vitro CEA-rele ase assay, we determined that a factor in human and fetal bovine sera signifrcantly augments the release of CEA from the tumor cell surface into cell culture supernatants. Results: As little as 1% serum admired 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 electrophor etic mobility and membrane linkage of CEA released by serum appear to be identical to those of CEA released by bacterial phospholipase C. Be cause bacterial phospholipase C is known specifically to cleave the ph osphoinositol (PI) glycan moiety that anchors CEA to the tumor cell su rface, a mechanism of action for serum cleaving this anchor is suggest ed. Conclusions: The large range of CEA levels observed in patients wi th colorectal cancers may be related to differential sensitivity of th e CEA membrane anchor to the CEA-releasing factor in serum.