Loss of metastatic and primary tumor factor X activator capabilities by Lewis lung carcinoma cells cultured in vitamin K-dependent protein deficient serum.
A highly metastatic line of Lewis lung tumor cells established in fetal bovine serum (10%) was subcultured into normal rodent (mouse or rat) serum or rodent serum made deficient in functional vitamin K-dependent proteins (barium sulfate adsorption or warfarin treatment of animals). Following injection of cells cultured in normal rodent serum into C57BL/6 mice, Factor X activator activity in the primary tumors increased at a near linear rate per gram tumor and attained 5- to 8-fold higher levels than did cells grown in either of the deficient sera. Secondary lung foci were also visible in all mice of the normal-rodent serum groups within 10 days after injection, and by 21 days extensive tumor growth in the lungs had developed. No secondary lung foci were apparent in any mice of the deficient serum groups throughout 21 days of tumor burden. Cells cultured in nonrodent serum (fetal bovine serum) were less proficient than cells grown in normal mouse serum in developing primary tumor Factor X activator activity and producing secondary tumors. Exposure of cells cultured in barium sulfate-treated mouse serum to normal mouse serum for 3 h and 3 weeks prior to injection partially restored primary tumor Factor X activator and metastatic competence. These data strongly suggest that in Lewis lung tumor cells at least one species selective, plasma/serum vitamin K-dependent protein plays a major role in the regulation of metastatic events and demonstrate that there is a positive correlation between primary tumor Factor X activation activity and metastasis.
Fasco
M J
MJ
Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201-0509.
Eagan
G E
GE
Wilson
A C
AC
Gierthy
J F
JF
Lincoln
D L
DL
D000818:Animals; D001798:Blood Proteins / Q000502:physiology*; D003029:Coagulants / Q000032:analysis*; D003546:Cysteine Endopeptidases / Q000032:analysis*; D005170:Factor X / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins; D009374:Neoplasms, Experimental / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014812:Vitamin K / Q000494:pharmacology*
D001798:Blood Proteins; D003029:Coagulants; D009363:Neoplasm Proteins; D014812:Vitamin K; D005170:Factor X; D003546:Cysteine Endopeptidases; C030910:cancer procoagulant