Involvement of circulating CEA in liver metastases from colorectal cancersre-examined in a new experimental model

Both experimental and clinical data show evidence of a correlation between elevated blood levels of carcinoembryonic antigen (CEA) and the development of liver metastases from colorectal carcinomas. However, a cause-effect re lationship between these two observations has not been demonstrated. For th is reason, we developed a new experimental model to evaluate the possible r ole of circulating CEA in the facilitation of liver metastases. A CEA-negat ive subclone from the human colon carcinoma cell line CO115 was transfected either with CEA-cDNA truncated at its 3' end by the deletion of 78 base pa irs leading to the synthesis of a secreted form of CEA or with a full-lengt h CEA-cDNA leading to the synthesis of the entire CEA molecule linked to th e cell surface by a GPI anchor. Transfectants were selected either for thei r high CEA secretion (clone CO115-2C2 secreting up to 13 mu g CEA per 10(6) cells within 72 h) or for their high CEA membrane expression (clone CO115- 5F12 expressing up to 1 x 10(6) CEA molecules per cell). When grafted subcu taneously, CO115-2C2 cells gave rise to circulating CEA levels that were di rectly related to the tumour volume (from 100 to 1000 ng ml(-1) for tumours ranging from 100 to 1000 mm(3)), whereas no circulating CEA was detectable in CO115 and CO115-5F12 tumour-bearing mice. Three series of nude mice bea ring a subcutaneous xenograft from either clone CO115-2C2 or the CO115-5F12 transfectant, or an untransfected CO115 xenograft, were further challenged for induction of experimental liver metastases by intrasplenic injection o f three different CEA-expressing human colorectal carcinoma cell lines (LoV o, LS174T or CO112). The number and size of the liver metastases were shown to be independent of the circulating CEA levels induced by the subcutaneou s CEA secreting clone (CO115-2C2), but they were directly related to the me tastatic properties of the intrasplenically injected tumour cells.