Comparative Studies on Protein Turnover Regulations in Tumor Cells and Host Tissues: Development and Analysis of an Experimental Model

The protein mass of cells and tissues is determined by the relative rates of protein synthesis (PS) and degradation (PD). A convergent modulation of both PS and PD is operated by many cell types to regulate protein accumulation and thus growth. Transformed and neoplastic cells may show markedly defective PD regulations. Yet even highly-deviated cells such as those of the transplantable Yoshida ascites hepatoma AH-130 cease growth when attaining a conspicuous population size, by operating a combined reduction of PS and acceleration of PD. As in normal cells, PD acceleration is effected through an activation of the acidic-vacuolar (lysosomal) mechanism. AH-130 tumor-bearing rats develop a markedly negative nitrogen balance early after transplantation. Tumor growth involves pronounced perturbations in host body and tissue protein metabolism. Apparently, these changes occur mostly at the level of PD rather than PS, at least in liver and skeletal muscle (gastrocnemius). These observations indicate that either tumor and host cells sense different signals for PD regulations or their thresholds for the same signals are poised differently. This model seems most suitable for further studies to elucidate which signals and mechanisms are involved in these protein metabolic perturbations and possibly, to develop the rationale for adequate corrective strategies.