UP-REGULATION OF PERIPHERAL BENZODIAZEPINE RECEPTOR SYSTEM IN HEPATOCELLULAR-CARCINOMA

Increased number of peripheral benzodiazepine receptors (PBRs) have be en found in some tumors outside the liver. The present study was to ve rify whether the PER system is altered in hepatocellular carcinoma (HC C). The levels of endogenous benzodiazepine-like compounds (BZDs), mea sured by radioreceptor binding technique after HPLC purification and t he endogenous ligand for PBRs, termed diazepam binding inhibitor (DBI) , measured by radioimmunoassay utilizing a specific antibody for human DBI, were studied in the blood of 15 normal subjects, 12 liver cirrho sis and 10 patients with HCC. The levels of BZDs in serum were increas ed hundred fold in liver cirrhosis patients and slightly elevated in H CC patients. DBI was found to be increased in HCC patients. The bindin g recognition sites for PBRs (B-max) were increased 4 to 7 fold in HCC tissue in comparison with that found in non-tumoral liver tissue (NTL T). On the contrary the concentrations of DBI were found to be signifi cantly decreased in HCC tissue in Comparison with the respective NTLT. These results seem to suggest an implication of PBRs and of their put ative endogenous ligands in the metabolism of these neoplastic cells a nd possibly in their proliferation. The up-regulation of PBRs found in HCC tissue seems to indicate an increased functional activity of thes e receptors and opens up the possibility of new pharmacological and di agnostic approaches while the changes in the circulating endogenous li gands for the above receptors might be envisaged as early markers of t umorigenesis in liver cirrhosis.