Protein turnover states of tumour cells and host tissues in an experimental model.

To investigate the progress of tissue protein metabolic perturbations in animals developing cancer cachexia, we analyzed an experimental model system based on a highly-deviated, transplantable ascites hepatoma of the rat (Yoshida AH-130). After inoculation, at first this tumour grew rapidly at an exponential rate, then it entered a stationary state until animal death (in about 15 days). Cessation of protein accumulation (growth) was achieved by tumour cells thanks to a combined reduction of synthesis and enhancement of protein degradation (slow-turnover protein pool); the latter was apparently operated through activation of the acidic vacuolar (lysosomal) mechanism. The body weight, net of tumour, early and progressively declined in transplanted rats. Their liver initially showed a moderate enlargement, mostly accounted for by a reduction in the protein breakdown rate; then the liver eventually atrophied, in spite of an enhanced synthetic rate, because of an even greater increase of the degradative rate. By contrast, gastrocnemius muscles started loosing weight and protein since the early phases of tumour growth; their atrophy was associated with elevation of the apparent protein degradative rate, with no change in the apparent synthetic rate. Therefore, tumour growth somehow elicited perturbations in the host tissues examined, which apparently mostly affected the catabolic side of protein turnover.