Therapeutic Discovery Prognostic Role of KiSS-1 and Possibility of Therapeutic Modality of Metastin, the Final Peptide of the KiSS-1Gene, in Urothelial Carcinoma
نویسندگان
چکیده
TheKiSS-1 gene has been reported to be ametastasis suppressor gene in humanmelanoma. Thegene product was isolated from human placenta as the ligand of GPR54, a G protein–coupled receptor, and the C-terminally amidated peptide of 54 amino acids is called metastin. The binding of metastin to GPR54 has been shown to inhibit tumormetastasis in some tumor cells; however, its function remains unclear in urothelial carcinoma.We first evaluated KiSS-1 expression and GPR54 expression in 151 patients with upper urinary tract urothelial carcinoma todetermine theirprognostic significance.Next,weexamined the roleofmetastin in the invasiveness and lung metastasis of MBT-2 variant (MBT-2V), which is a highly metastatic murine bladder cancer cell. Multivariate analysis revealed that KiSS-1 expression was an independent predictor of metastasis and overall survival. However, GPR54 expression was not selected. Hematogeneous metastasis had a significantly lower level of KiSS-1 expression comparedwith lymph nodemetastasis. Metastin treatment significantly reduced the invasiveness of MBT-2V cells and inhibited the DNA-binding activity of NF-kB by blocking its nuclear translocation, leading to a reduction in the expression and activity of matrix metalloproteinase-9. Metastin treatment dramatically prevented the occurrence of lung metastatic nodules (6.3 2.3, n1⁄4 15) compared with controls (30.4 5.1, n 1⁄4 15; P < 0.01), as well as had survival benefit. KiSS-1 plays an important role in the prognosis of upper tract urothelial carcinoma and metastin may be an effective inhibitor of metastasis in urothelial carcinoma through its blockade of NF-kB function. Mol Cancer Ther; 11(4); 853–63. 2012 AACR.
منابع مشابه
P-222: Expression of RFamide-Related Peptide-3 and KiSS-1 mRNA in The Hypothalamus of Pregnant Rat
Background: There is no follicular development during pregnancy in the rat comparable to the changes of the estrous cycle. RFamide-related peptide-3 (RFRP-3) and kisspeptin were recognized as regulator of gonadotropin releasing hormone (GnRH) and luteinizing hormone (LH) secretion in several species, including the rat. The aim of the present study was to evaluate the relative expression of RFRP...
متن کاملExpression of RFamide-Related Peptide-3 (RFRP-3) mRNA in Dorsomedial Hypothalamic Nucleus and KiSS-1 mRNA in Arcuate Nucleus of Rat during Pregnancy
متن کامل
The effect of ghrelin on Kiss-1 and KissR gene transcription and insulin secretion in rat islets of Langerhans and CRI-D2 cell line
Objective(s): Ghrelin is a peptide hormone that has been shown to have numerous central and peripheral effects. The central effects including GH secretion, food intake, and energy homeostasis are partly mediated by Kiss1- KissR signaling pathway. Ghrelin and its receptor are also expressed in the pancreatic islets. Ghrelin is one of the key metabolic factors controlling insulin secretion from t...
متن کاملLong term malnutrition and mRNAs expression of RFRP-3 and KiSS-1 in hypothalamus of female ovariectomized rats
Introduction: Arginine-phenylalanine-amide-related peptide-3 (RFRP-3) is an inhibitor of gonadotropin releasing hormone (GnRH) secretion and an appetizer. Kisspeptin is a stimulator of GnRH and a regulator of energy metabolism. The objectives of the present study were to compare the effect of long term malnutrition on expression of RFRP-3 mRNA in dorsomedial hypothalamic nucleus (DMH) and Ki...
متن کاملLactation effect on the mRNAs expression of RFRP-3 and KiSS-1 in dorsomedial and arcuate nuclei of the rat hypothalamus
Introduction: Arginine-phenylalanine-amide-related peptide-3 (RFRP-3) and kisspeptin are believed to be inhibitor and stimulator of gonadotropin releasing hormone (GnRH) secretion, respectively. The aim of the present study was to compare the effect of lactation on the expression of RFRP-3 mRNA in dorsomedial hypothalamic nucleus (DMH) and KiSS-1 mRNA in arcuate nucleus (ARC) of hypothalamus...
متن کامل