Plasma albumin concentration declines in both experimental and clinical
cancer. Previous investigations have demonstrated that this is partly explained by increased breakdown of
albumin. The present study has identified the tissue sites for increased
albumin degradation in a nonmetastasizing
sarcoma mouse (C57/BL6J) model. Results have been compared to nontumor-bearing animals either freely fed or food restricted (pair-weighed) so that their body composition was similar to
tumor-bearing animals.
Tumor-bearing mice had increased
albumin degradation (0.13 +/- 0.02 mg/hr/g bw) compared to both freely fed (0.09 +/- 0.007) and pair-weighed control animals (0.05 +/- 0.008). Radioactivity from circulating [3H]raffine
aldehyde labeled
albumin appeared with maximum peak values in lysosomes isolated from both
tumor and nontumor tissues at 48 hr following iv injection. The intralysosomal accumulation of radioactivity was two- to threefold higher in
tumor tissue compared to liver tissue, although the specific activity of
protease(s) for
albumin degradation measured in vitro was not higher in
tumor tissue (30.4 +/- 3.6 mg/hr/g tissue) compared to normal liver tissue (36.9 +/- 1.7). Accounting for the entire
tumor the proteolytic capacity for
albumin breakdown was however much larger in the
tumor (161.6 +/- 32.6 mg/organ) compared to both normal liver (37.5 +/- 2.3) and
tumor-host liver (56.4 +/- 2.8).
Pepstatin inhibited 78 +/- 6% of the proteolytic activity in the
tumor measured by 125I-labeled undenatured mouse
albumin as the substrate.
Leupeptin inhibited 49 +/- 6%. There was a significantly decreased breakdown of
albumin in both skeletal muscles and the gastrointestinal tract from
tumor-bearing animals.(ABSTRACT TRUNCATED AT 250 WORDS)