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Gut 45:766-774 doi:10.1136/gut.45.5.766
  • Liver disease

Regulatory peptide receptors in human hepatocellular carcinomas

  1. J C Reubia,
  2. A Zimmermanna,
  3. S Jonasb,
  4. B Wasera,
  5. P Neuhausb,
  6. U Läderacha,
  7. B Wiedenmannc
  1. aInstitute of Pathology, University of Berne, Berne, Switzerland, bDepartment of Surgery, Humboldt University, Berlin, Germany, cDepartment of Internal Medicine, Humboldt University, Berlin, Germany
  1. Dr J C Reubi, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Murtenstrasse 31, PO Box 62, CH-3010 Berne, Switzerland.
  • Accepted 11 May 1999

Abstract

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 peptide (VIP), substance P, cholecystokinin (CCK) A and B, and neurotensin receptors 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 HCC.

RESULTS 41% of HCC expressed somatostatin receptors; 47% expressed VIP receptors. VIP receptors were always identified in non-neoplastic liver tissue. Substance P receptors were only identified in 5% of HCC but in the majority of their peritumorous and intratumorous vessels. CCK-A and -B and neurotensin receptors were not detected in HCC. The somatostatin receptors showed high affinity for somatostatin and octreotide. The VIP receptors had high affinity for VIP, pituitary adenylate cyclase activating peptide (PACAP) 27, and a VIP1 selective analogue, suggesting the presence of VIP1/PACAP II type receptors. PACAP I receptors were identified in two cases. Substance P receptors were all of the NK1 subtype. The density of somatostatin receptors in HCC was low compared with the density found in liver metastases of neuroendocrine tumours. The VIP receptor density was 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 mediate tumour growth. Diagnostic and therapeutic evaluation of somatostatin and VIP analogues may be of interest in receptor positive HCC.

Footnotes

  • Abbreviations used in this paper:
    BSA
    bovine serum albumin
    CCK
    cholecystokinin
    HCC
    hepatocellular carcinoma
    125I-BHSP
    Bolton-Hunter substance P
    [LTT]-SS-28
    [Leu8,d-Trp22,Tyr25]- somatostatin 28
    NK
    neurokinin
    PACAP
    pituitary adenylate cyclase activating peptide
    VIP
    vasoactive intestinal peptide