Gonadotropin-Releasing Hormone Induces Actin Cytoskeleton Remodeling and Affects Cell Migration in a Cell-Type-Specific Manner in TSU-Pr1 and DU145 Cells

Abstract

GnRH was first identified as the hypothalamic decapeptide that promotes gonadotropin release from pituitary gonadotropes. Thereafter, direct stimulatory and inhibitory effects of GnRH on cell proliferation were demonstrated in a number of types of primary cultured cells and established cell lines. Recently, the effects of GnRH on cell attachment, cytoskeleton remodeling, and cell migration have also been reported. Thus, the effects of GnRH on various cell activities are of great interest among researchers who study the actions of GnRH. In this study, we demonstrated that GnRH induces actin cytoskeleton remodeling and affects cell migration using two human prostatic carcinoma cell lines, TSU-Pr1 and DU145. In TSU-Pr1, GnRH-I and -II induced the filopodia formation of the cells and promoted cell migration, whereas in DU145, GnRH-I and -II induced the formation of the cells with stress fiber and inhibited cell migration. In our previous studies, we reported the stimulatory and inhibitory effects of GnRH on the cell proliferation of TSU-Pr1 and DU145 cells. This study provides the first evidence for the effects of GnRH on actin cytoskeleton remodeling and cell migration of cells in which cell proliferation was affected by GnRH at the same time. Moreover, we also demonstrated that the same human GnRH receptor subtype, human type I GnRH receptor, is essential for the effects of GnRH-I and -II on actin cytoskeleton remodeling and cell migration in both TSU-Pr1 and DU145 cells using the technique of gene knock-down by RNA interference.

Gonadotropin-releasing hormone agonists reduce the migratory and the invasive behavior of androgen-independent prostate cancer cells by interfering with the activity of IGF-I

“…Similar results have been reported by these authors for GnRH-II. The reasons for the discrepancy between the data by Enomoto and coworkers (37) and those reported in the present study probably reside in the many differences encountered in the methodology applied. First of all, the migration assay, based on the Boyden's chamber technique, has been developed in different experimental conditions.…”

“…Moreover, Dondi and coworkers (31) have reported that Leuprolide exerts an anti-metastatic activity on androgen-independent prostate cancer cells, through the inhibition of the urokinse plasminogen activator (uPA) system. However, the results seem to diverge, at least partially, from those recently published by Enomoto et al (37). These authors have studied the effects of GnRH and of the second form of GnRH recently found in mammals (GnRH-II) (38)(39)(40)(41) on the motility of two prostate cancer cell lines (TSU-Pr1 and DU 145), by utilizing a modified Boyden's chamber.…”

Gonadotropin-Releasing Hormone Promotes Ovarian Cancer Cell Invasiveness through c-Jun NH2-Terminal Kinase–Mediated Activation of Matrix Metalloproteinase (MMP)-2 and MMP-9

“…In prostate cancer, GnRH has been shown to regulate cell motility through its interaction with the small GTPases Rac1, Cdc42, and RhoA, which are involved in the regulation of actin polymerization (32). Our data show that another mechanism by which GnRH may promote tumor cell migration and invasion is through increased expression and proteolytic activities of MMP-2 and MMP-9 that specifically degrade the basement membrane.…”

Human gonadotropin-releasing hormone receptor-activated cellular functions and signaling pathways in extra-pituitary tissues and cancer cells (Review)

“…In the DU145 cell, GnRHa was able to inhibit fibroblast growth factor (FGF)-stimulated cell proliferation, invasion and the ability of these cells to recover from a cytotoxic insult by exposure to etoposide, a topoisomerase II inhibitor (108). In TSU-Pr1 cells, GnRH induced filopodia formation and increases cell migration, while in DU145 cells this hormone promotes stress-fiber formation and abolishes cell migration (114). In this latter case, the mechanism activated by GnRH to regulate cell migration and actin cytoskeleton was related with small G protein from the Rho family (Fig.…”