Regulatory peptide receptors in human hepatocellular carcinomas

Background-Overexpression of regulatory peptide receptors in selected human tumours is of diagnostic and therapeutic relevance. Aims-To evaluate the expression of somatostatin, vasoactive intestinal pept ide (VIP), substance P, cholecystokinin (CCK) A and B, and neurotensin rece ptors in hepatocellular carcinoma (HCC). Methods-In vitro receptor autoradiography for the various peptide receptors using selective iodinated radioligands on tissue sections in 59 cases of H CC. Results-41% of HCC expressed somatostatin receptors; 47% expressed VIP rece ptors, VIP receptors were always identified in non-neoplastic liver tissue, Substance P receptors were only identified in 5% of HCC but in the majorit y of their peritumorous and intratumorous vessels. CCK-A and -B and neurote nsin receptors were not detected in HCC. The somatostatin receptors showed high affinity for somatostatin and octreotide. The VIP receptors had high a ffinity for VIP, pituitary adenylate cyclase activating peptide (PACAP) 27, and a VIP1 selective analogue, suggesting the presence of VIP1/PACAP IZ ty pe receptors. PACAP I receptors were identified in two cases. Substance P r eceptors were all of the NK1 subtype. The density of somatostatin receptors in HCC was low compared with the density found in liver metastases of neur oendocrine tumours, The VIP receptor density ws always lower in HCC than in adjacent liver tissue. Conclusions-Somatostatin, VIP, and substance P may have a receptor mediated role in HCC. Substance P receptors may be involved in regulation of tumour associated blood flow; somatostatin receptors and VIP receptors may mediat e tumour growth. Diagnostic and therapeutic evaluation of somatostatin and VIP analogues may be of interest in receptor positive HCC.