SIALYLTRANSFERASE ACTIVITY AND HEPATIC TUMOR-GROWTH IN A NUDE-MOUSE MODEL OF COLORECTAL-CANCER METASTASES

Sialyltransferase activity (EC 2.4.99.6) was measured in the microsoma l fraction of colorectal cancer cell lines using an assay based on the incorporation of [C-14]CMP-sialic acid into asialofetuin. In the poor ly differentiated lines MIP101 and Clone A, sialyltransferase activity had a V(max) of 0.36 and 0.31 nmol/mg protein/h, respectively, while the moderately differentiated to well-differentiated cell lines HT-29, CCL188, and CX-1 had V(max)s of 2.46, 1.05, and 1.24 nmol/mg protein/ h, respectively. All cell lines tested had a K(m) of 15.4 (+/- 0.7)(SD )-mu-mol/liter. The better differentiated cells had higher levels of s ialyltransferase activity, which correlated with their higher levels o f sialic acid and their enhanced ability to form liver metastases in t he nude mouse following intrasplenic injection compared to the poorly differentiated cell lines. Treatment of the cell lines with KI-8110, a CMP-sialic acid derivative which prevents incorporation of sialic aci d into glycoconjugates, resulted in reduced formation of hepatic metas tases by the colorectal carcinoma cell lines in the nude mouse model. It is suggested that reduced sialylation of adhesion molecules such as carcinoembryonic antigen may change the biology of the tumor cell, on e consequence of which is the prevention of implantation of the cells into distant sites, resulting in a reduced incidence of metastases.