Inhibition of sialic acid incorporation prevents hepatic metastases.
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.
Wagner
H E
HE
Department of Surgery, New England Deaconess Hospital, Harvard Medical School, Boston, Mass.
Thomas
P
P
Wolf
B C
BC
Rapoza
A
A
Steele
G
G
D000818:Animals; D002272:Carcinoembryonic Antigen / Q000032:analysis; D002460:Cell Line / Q000187:drug effects / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism; D006027:Glycosides / Q000494:pharmacology; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000378:metabolism / Q000517:prevention & control / Q000556:secondary*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012794:Sialic Acids / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014529:Uridine / Q000031:analogs & derivatives / Q000494:pharmacology
D002272:Carcinoembryonic Antigen; D006027:Glycosides; D008562:Membrane Glycoproteins; D012794:Sialic Acids; C047714:KI 8110; D014529:Uridine