Inhibitory effects of antagonists of growth hormone releasing hormone (GHRH) in thyroid cancer

A team of Ipatimup/i3S researchers in collaboration with researchers from Sylvester Comprehensive Cancer Center and Interdisciplinary Stem Cell Institute of Miami published a study in Hormones and Cancer and researchers presently at the Federal University of Rio de Janeiro (UFRJ), where they evaluated the effect of two new GHRH antagonists, MIA602 and MIA690, on thyroid cancer, using in vitro and in vivo models. They demonstrate 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.

Authors and Affiliations:

Helena Pópulo^1,2*, Bruno Nunes^1,2,§*, Cristina Sampaio^1,2, Rui Batista^1,2,3, Marta Teixeira Pinto^,1,2, Tiago B. Gaspar^1,2, Leandro Miranda-Alves^1,2,§, Ren-Zhi Cai^4,6, Xian Yang Zhang^4,6, Andrew V. Schally^4,5,6, Manuel Sobrinho-Simões^1,2,7,8, Paula Soares^1,2,7

¹ Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto, Portugal

² Institute for Research and Innovation in Health (I3S), University of Porto, Porto, Portugal (Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal)

³ Medical Faculty, University of Porto, Porto, Portugal

⁴ Veterans Affairs Medical Center Miami, Miami, FL, USA

⁵ Department of Pathology, ⁶ Department of Medicine, Divisions of Endocrinology and Hematology-Oncology, Sylvester Comprehensive Cancer Center and Interdisciplinary Stem Cell Institute, University of Miami, School of Medicine, Miami, FL, USA

⁷ Department of Pathology and Oncology, Medical Faculty, University of Porto, Porto, Portugal

⁸ Department of Pathology, Hospital S. João, Porto, Portugal

^§- Present address: Experimental Endocrinology-GPEEx Group, Institute of Biomedical Sciences and Postgraduate Endocrinology, Medical Faculty, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

*- These authors contributed equally

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.

Journal: Hormones and Cancer

Link: https://link.springer.com/article/10.1007%2Fs12672-017-0307-4