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

Abstract

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.

Hyperlipemia: a role in regulating UCP3 gene expression in skeletal muscle during cancer cachexia?

“…Its growth in the host causes rapid and progressive loss of body weight and tissue wasting, particularly in skeletal muscle. Acceleration of tissue protein breakdown accounts for most of the wasting in AH‐130 bearers [48,50–52]. In particular, skeletal muscle hypercatabolism involves hyperactivation of the ATP‐ubiquitin‐dependent proteolytic system [53].…”

Estimation of metabolic flux rates in liver purine catabolism of tumour‐bearing mice by computer simulation of radioactive tracer experiments

“…The interest of research dealing with the tumour-host organ interrelationships was directed mainly, in clinical studies, to the nutritional support of the cancer-bearing hostz5 and, in experimental studies, to the availability of nutrients and to the nutritive competition for the substrates by the tumour cells. [26][27][28] In ascites tumour-bearing mice one can observe an increase of the tumour mass, i.e. of the ascites cells plus the peritoneal ascites fluid, and therefore, also of the whole body mass of the animal, but a simultaneous decrease of the skeletal muscle mamZ9…”