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 microsomal fraction of colorectal cancer cell lines using an assay based on the incorporation of [14C]CMP-sialic acid into asialofetuin. In the poorly differentiated lines MIP101 and Clone A, sialyltransferase activity had a Vmax 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 Vmaxs of 2.46, 1.05, and 1.24 nmol/mg protein/h, respectively. All cell lines tested had a Km of 15.4 (+/- 0.7)(SD) mumol/liter. The better differentiated cells had higher levels of sialyltransferase activity, which correlated with their higher levels of sialic acid and their enhanced ability to form liver metastases in the 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 acid into glycoconjugates, resulted in reduced formation of hepatic metastases 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, one consequence of which is the prevention of implantation of the cells into distant sites, resulting in a reduced incidence of metastases.
Harvey
B E
BE
Department of Surgery, New England Deaconess Hospital, Harvard Medical School, Boston, Massachusetts 02115.
Toth
C A
CA
Wagner
H E
HE
Steele
G D
GD
Thomas
P
P
D000818:Animals; D002460:Cell Line; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D006801:Humans; D007700:Kinetics; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D012004:Rectal Neoplasms / Q000201:enzymology* / Q000473:pathology*; D012794:Sialic Acids / Q000032:analysis; D012799:Sialyltransferases / Q000302:isolation & purification / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D013384:Succinate Cytochrome c Oxidoreductase / Q000378:metabolism; D014183:Transplantation, Heterologous
D012794:Sialic Acids; D013384:Succinate Cytochrome c Oxidoreductase; D009251:NADPH-Ferrihemoprotein Reductase; D012799:Sialyltransferases; C029156:N-acetyllactosaminide alpha-2,3-sialyltransferase