Inhibitory Effects of Antagonists of Growth Hormone-Releasing Hormone (GHRH) in Thyroid Cancer

Helena Pópulo, Bruno Nunes, Cristina Sampaio, Rui Batista, Marta Teixeira Pinto, Tiago B. Gaspar, Leandro Miranda-Alves, Ren Zhi Cai, Xian Yang Zhang, Andrew V Schally, Manuel Sobrinho-Simões, Paula Soares

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Growth hormone-releasing hormone (GHRH) is a peptide hormone secreted by the hypothalamus that regulates the synthesis and secretion of growth hormone (GH) in the pituitary. The extra-hypothalamic GHRH and its cognate receptors (GHRHR and splice variants) play a mitogenic role by stimulating cell proliferation and preventing apoptotic cell death. It is well established that GHRH antagonists inhibit the growth, tumorigenicity, and metastasis of various human malignancies. In this work, we studied the effect of two new GHRH antagonists, MIA602 and MIA690, on thyroid cancer. We studied the effect of MIA602 and MIA690 on thyroid cancer in vitro, using human thyroid cancer cell lines, and in vivo, using chicken embryo chorioallantoic membrane (CAM) assays. We found that mRNA for GHRH and GHRH receptor is expressed in thyroid cell lines and in samples of thyroid tumors. Immunohistochemistry confirmed the expression of GHRHR protein in specimens of thyroid tumor. We observed that GHRH antagonists inhibited the growth and increased apoptosis of thyroid cancer cells. In vivo, the antagonists inhibited growth and angiogenesis of engrafted thyroid tumors. Our results suggest that GHRH expression may play a role in growth of thyroid cancer and that GHRH antagonists can be a therapeutic option for thyroid cancer patients.

Original languageEnglish (US)
Pages (from-to)314-324
Number of pages11
JournalHormones and Cancer
Volume8
Issue number5-6
DOIs
StatePublished - Dec 1 2017

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Keywords

  • GHRH antagonists
  • Growth hormone-releasing hormone
  • Hypothalamic hormone
  • mRNA for GHRH
  • mRNA for GHRH receptors
  • Thyroid cancer

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cancer Research

Cite this

Pópulo, H., Nunes, B., Sampaio, C., Batista, R., Pinto, M. T., Gaspar, T. B., Miranda-Alves, L., Cai, R. Z., Zhang, X. Y., Schally, A. V., Sobrinho-Simões, M., & Soares, P. (2017). Inhibitory Effects of Antagonists of Growth Hormone-Releasing Hormone (GHRH) in Thyroid Cancer. Hormones and Cancer, 8(5-6), 314-324. https://doi.org/10.1007/s12672-017-0307-4