Inhibition of sialic acid incorporation prevents hepatic metastases
H. E. Wagner, P. Thomas, B. C. Wolf, A. Rapoza and G. Steele Jr
Department of Surgery, New England Deaconess Hospital, Harvard Medical School, Boston, Mass.
It has been hypothesized that the metastatic capacity of tumors may be
correlated with hypersialylation of the cell surface. We used a novel
inhibitor of sialic acid incorporation, KI-8110, to determine the effect of
depletion of cell surface sialic acid on the metastatic behavior of three
human colorectal cancer cell lines, in which hepatic seeding was related to
tumor cell differentiation. Treatment of tumor cells with KI-8110 prior to
intrasplenic injection prevented liver colonization. Total cellular sialic
acid was reduced, as was that of the cell surface. Secreted forms of
carcinoembryonic antigen also were depleted of sialic acid by this
treatment. These data show that depletion of sialic acid from cell surface
glycoconjugates reduces the incidence of hepatic metastases from human
colorectal primary tumors and adds to the mounting evidence of the
importance of sialic acid in determining the biological behavior of tumor
cells.