Abstract
By use of a biochemical assay, we detected the existence in blood plasma of tumor-bearing rats the presence of factor(s) low or absent in normal rat plasma. The present report describes parameters which influence the appearance of this factor during carcinogenesis and development and also demonstrates its presence in the plasma of human cancer patients. The “plasma factor” was detectable within 48 hr of treatment of rats with a carcinogenic regimen of dimethylnitrosamine or thioacetamide. The activity in this initial transient phase, which was maximal at 3 weeks, was followed by a second progressive increase in activity, which, after 8 to 10 months, attained a level 5 to 6 times the initial increase. The latter persistent increase appears to parallel tumorigenesis. The factor showed a small and very transient increase during the early stages of liver regeneration after two-thirds partial hepatectomy or CCI4 intoxication, with normalization of the plasma activity within 15 days. The appearance of the factor in circulation coincided with that of a Mr 60,000 phosphoprotein. A factor with similar activity has been detected in the conditioned culture medium in which human cancer cells were grown and was present in significant concentration in the plasma of 100 cancer patients with a wide variety of primary (and metastatic) tumors. On Sepharose 6B chromatography, it appeared to have a Mr of about 70,000. The factor was absent or low in nonconditioned medium, in the plasma of normal controls and in patients free of active cancer (i.e., leukemia patients in remission). The plasma factor(s) appears to be an embryonic protein, since a protein(s) with similar activity is present in the plasma of pregnant rats at 14-day gestation and in the blood of the newborn rat; the factor rapidly disappears postpartum, reaching control levels by 4 days.
Supported by a grant from the Ohio Division of the American Cancer Society and by Grant CA 30627 to the authors; also supported by Grant P-30-CA-1605809 to Ohio State University Comprehensive Cancer Center from the NIH, Department of Health and Human Services.