Characterization of growth-inhibitory activities associated with an alpha-macroglobulin of mice.
An alpha-macroglobulin (AMG) of similar size and proteinase-binding activity as those of human, alpha 2-macroglobulin was purified to homogeneity from mouse plasma. Even after additional purification steps, AMG still retains a growth-inhibitory activity and a more complex subunit structure than does human alpha 2-macroglobulin. AMG can inhibit the DNA synthesis of all types of murine tumor cells tested in vitro. This activity is cytostatic, dose dependent, and unaffected by the serum concentration in culture. Because this inhibitory activity is resistant to heat, pH 3, and methylamine, it is apparently unrelated to the proteinase-binding activity which is labile to all these treatments. Furthermore, in contrast to the proteinase-binding activity, the inhibitory activity can be partially removed from AMG by acid dialysis. Gel filtration of the dialysate yields two fractions (Mr 12,000 and 1,000 to 5,000) which potently inhibit murine tumor cells but stimulate both the B- and T-lymphocyte reactivities to mitogens in vitro. The growth-inhibitory activities in these fractions are resistant to digestions by chymotrypsin, RNase, and DNase. We conclude from this study that AMG does not inhibit tumor growth by virtue of its proteinase-binding activity; it may inhibit tumor cells via the small biomediators it carries.
D000818:Animals; D002460:Cell Line; D002850:Chromatography, Gel; D002918:Chymotrypsin; D004247:DNA / Q000096:biosynthesis*; D003851:Deoxyribonucleases; D003956:Dialysis; D005260:Female; D006131:Growth Inhibitors / Q000302:isolation & purification*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding; D012260:Ribonucleases; D014357:Trypsin / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology
D006131:Growth Inhibitors; D000511:alpha-Macroglobulins; D004247:DNA; D003851:Deoxyribonucleases; D012260:Ribonucleases; D002918:Chymotrypsin; D014357:Trypsin