Characterization of receptors for growth hormone-releasing hormone in human osteosarcomas and Ewing's sarcomas

  • Authors:
    • Gabor Halmos
    • Andrew V. Schally
    • Andrea L.F. Bernardino
    • Jozsef L. Varga
  • View Affiliations

  • Published online on: August 1, 2006     https://doi.org/10.3892/ijo.29.2.463
  • Pages: 463-469
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Abstract

Antagonists of growth hormone-releasing hormone (GH-RH) inhibit growth of various human cancers including osteosarcomas and Ewing's sarcomas, xenografted into nude mice or cultured in vitro. The antiproliferative effect of GH-RH antagonists could be mediated, in part, through the splice variants (SVs) of receptors for GH-RH which have been found in several human cancers and cancer cell lines. In this study we investigated the expression of SVs of GH-RH receptors and the binding characteristics of these receptor isoforms in MNNG/HOS human osteosarcoma and SK-ES-1 human Ewing's sarcoma grown in nude mice. RT-PCR revealed the presence of mRNA for SVs of GH-RH receptors in both human malignant bone cancer models. Using ligand competition assays with 125I-labeled GH-RH antagonist JV-1-42, we demonstrated in MNNG/HOS and SK-ES-1 tumors the presence of specific high affinity binding sites for GH-RH (Kd=5.83 nM and Kd=2.76 nM) with a maximal binding capacity (Bmax) of 552.1 fmol/mg protein and 371.9 fmol/mg protein, respectively. We also investigated the effect of GH-RH antagonist JV-1-38, administered s.c. at a dose of 20 µg twice daily for 4 weeks on the gene expression, affinity and concentration of receptors for GH-RH in MNNG/HOS human osteosarcomas xenografted into nude mice. Treatment with JV-1-38 did not affect the expression and binding characteristics of GH-RH receptors. High affinity binding of JV-1-38 to GH-RH receptors on MNNG/HOS tumors was characterized by an IC50 value of 1.04 nM. The presence of GH-RH receptors in human bone tumors provides a rationale for new approaches to the therapy of this malignancy based on GH-RH antagonists.

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August 2006
Volume 29 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Halmos, G., Schally, A.V., Bernardino, A.L., & Varga, J.L. (2006). Characterization of receptors for growth hormone-releasing hormone in human osteosarcomas and Ewing's sarcomas. International Journal of Oncology, 29, 463-469. https://doi.org/10.3892/ijo.29.2.463
MLA
Halmos, G., Schally, A. V., Bernardino, A. L., Varga, J. L."Characterization of receptors for growth hormone-releasing hormone in human osteosarcomas and Ewing's sarcomas". International Journal of Oncology 29.2 (2006): 463-469.
Chicago
Halmos, G., Schally, A. V., Bernardino, A. L., Varga, J. L."Characterization of receptors for growth hormone-releasing hormone in human osteosarcomas and Ewing's sarcomas". International Journal of Oncology 29, no. 2 (2006): 463-469. https://doi.org/10.3892/ijo.29.2.463