Expression of neuropeptide hormone receptors in human adrenal tumors and cell lines: Antiproliferative effects of peptide analogues

C. G. Ziegler, J. W. Brown, A. V. Schally, A. Erler, L. Gebauer, A. Treszl, L. Young, L. M. Fishman, J. B. Engel, H. S. Willenberg, S. Petersenn, G. Eisenhofer, M. Ehrhart-Bornstein, S. R. Bornstein

Research output: Contribution to journalArticle

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Abstract

Peptide analogues targeting various neuropeptide receptors have been used effectively in cancer therapy. A hallmark of adrenocortical tumor formation is the aberrant expression of peptide receptors relating to uncontrolled cell proliferation and hormone over-production. Our microarray results have also demonstrated a differential expression of neuropeptide hormone receptors in tumor subtypes of human pheochromocytoma. In light of these findings, we performed a comprehensive analysis of relevant receptors in both human adrenomedullary and adrenocortical tumors and tested the antiproliferative effects of peptide analogues targeting these receptors. Specifically, we examined the receptor expression of somatostatin-type-2 receptor, growth hormone-releasing hormone (GHRH) receptor or GHRH receptor splice variant-1 (SV-1) and luteinizing hormone-releasing hormone (LHRH) receptor at the mRNA and protein levels in normal human adrenal tissues, adrenocortical and adrenomedullary tumors, and cell lines. Cytotoxic derivatives of somatostatin AN-238 and, to a lesser extent, AN-162, reduced cell numbers of uninduced and NGF-induced adrenomedullary pheochromocytoma cells and adrenocortical cancer cells. Both the splice variant of GHRH receptor SV-1 and the LHRH receptor were also expressed in adrenocortical cancer cell lines but not in the pheochromocytoma cell line. The GHRH receptor antagonist MZ-4-71 and LHRH antagonist Cetrorelix both significantly reduced cell growth in the adrenocortical cancer cell line. In conclusion, the expression of receptors for somatostatin, GHRH, and LHRH in the normal human adrenal and in adrenal tumors, combined with the growth-inhibitory effects of the antitumor peptide analogues, may make possible improved treatment approaches to adrenal tumors.

Original languageEnglish (US)
Pages (from-to)15879-15884
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number37
DOIs
StatePublished - Sep 15 2009

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Keywords

  • Aberrant receptors
  • Cytotoxic peptide derivatives
  • Targeted therapy
  • Tumor endocrinology

ASJC Scopus subject areas

  • General

Cite this

Ziegler, C. G., Brown, J. W., Schally, A. V., Erler, A., Gebauer, L., Treszl, A., Young, L., Fishman, L. M., Engel, J. B., Willenberg, H. S., Petersenn, S., Eisenhofer, G., Ehrhart-Bornstein, M., & Bornstein, S. R. (2009). Expression of neuropeptide hormone receptors in human adrenal tumors and cell lines: Antiproliferative effects of peptide analogues. Proceedings of the National Academy of Sciences of the United States of America, 106(37), 15879-15884. https://doi.org/10.1073/pnas.0907843106