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
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Inhibitory Effects of Antagonists of Growth Hormone-Releasing Hormone (GHRH) in Thyroid Cancer.
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.
期刊介绍：
Hormones and Cancer is a unique multidisciplinary translational journal featuring basic science, pre-clinical, epidemiological, and clinical research papers. It covers all aspects of the interface of Endocrinology and Oncology. Thus, the journal covers two main areas of research: Endocrine tumors (benign & malignant tumors of hormone secreting endocrine organs) and the effects of hormones on any type of tumor. We welcome all types of studies related to these fields, but our particular attention is on translational aspects of research. In addition to basic, pre-clinical, and epidemiological studies, we encourage submission of clinical studies including those that comprise small series of tumors in rare endocrine neoplasias and/or negative or confirmatory results provided that they significantly enhance our understanding of endocrine aspects of oncology. The journal does not publish case studies.
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