title: Metastin receptor is overexpressed in papillary thyroid cancer and activates MAP kinase in thyroid cancer cells.
abstract: The development of distant metastasis is the most important predictor of death from thyroid cancer. KiSS-1 is a recently cloned human metastasis suppressor gene whose product, metastin, was recently identified as the endogenous agonist for a novel Gq/11 coupled receptor (metastin receptor). The expression and functional consequences of metastin and the metastin receptor have not been evaluated in thyroid cancer. We measured metastin and metastin receptor mRNA levels in 10 FCs and 13 papillary carcinomas (PCs), 2 benign non-functioning follicular adenomas (FAs), and 11 normal thyroid samples, and evaluated the signaling pathways activated by metastin in ARO thyroid cancer cells that express the metastin receptor endogenously. Paired normal and tumor samples were available for 4 PC and 3 PFC samples. Metastin mRNA was detected in 6/11 normal samples, and 0/2 FA, 2/10 FC, and 9/13 PC samples (p < 0.05 for PC vs. FC). Metastin receptor was not expressed in any normal thyroid or benign FA samples, and was expressed in only a minority (2/10) of FC samples. However, the receptor was expressed in the majority (10/13) of PCs (p = 0.002 for PC vs. normal tissue). Increased levels of metastin receptor were detected in all four PCs compared to adjacent normal tissue. Incubation levels of metastin receptor were detected in all four PCs compared to adjacent normal tissue. Incubation of metastin receptor expressing ARO thyroid cancer cells with metastin resulted in activation of ERK, but not Akt. Taken together, these data suggest a potential role for metastin and/or metastin receptors in modulating the biological behavior of thyroid cancers.
authors: Department of Medicine, Washington Hospital Center and MedStar Research Institute, Washington, D.C. 20010, USA. mathew.ringel@medstar.net
authors: Matthew D
authors: MD
authors: Ringel
authors: Elena
authors: E
authors: Hardy
authors: Victor J
authors: VJ
authors: Bernet
authors: Henry B
authors: HB
authors: Burch
authors: Frank
authors: F
authors: Schuppert
authors: Kenneth D
authors: KD
authors: Burman
authors: Motoyasu
authors: M
authors: Saji
mesh_terms: D002291:Carcinoma, Papillary / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D018013:Receptors, Neuropeptide; D012016:Reference Values; D013961:Thyroid Gland / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: C118688:KISS1R protein, human; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D000074502:Receptors, Kisspeptin-1; D018013:Receptors, Neuropeptide; D020928:Mitogen-Activated Protein Kinases