Inhibitory activity of luteinizing hormone-releasing hormone on tumor growth and progression.

Abstract

Luteinizing hormone-releasing hormone (LHRH) is the key hormone in the control of reproductive functions. In recent years, it has become evident that LHRH might act as a growth modulatory factor in tumors of the reproductive system. We have shown that in prostate cancer cells LHRH is expressed, together with its receptors, to negatively regulate cell proliferation. In these cells, LHRH acts as an antimitogenic factor through the activation of the Gi-cAMP intracellular signaling pathway. More recently, we investigated whether an LHRH-based autocrine system might also be expressed in tumors that are not classically related to the reproductive tract, such as melanoma. Malignant melanoma is known to be characterized not only by a high proliferation rate, but also by an aggressive metastatic behavior. We have demonstrated that both LHRH and LHRH receptors are expressed in human melanoma cells (BLM and Me15392). Activation of LHRH receptors by means of a potent LHRH agonist (Zoladex) significantly inhibited cell proliferation. The LHRH agonist also reduced the ability of melanoma cells to invade a reconstituted basement membrane (Matrigel) and to migrate in response to a chemotactic stimulus. These data indicate that: (a) in prostate cancer cells the LHRH receptor is coupled to a Gi-cAMP signal transduction pathway; (b) LHRH and LHRH receptors are also expressed in tumors that are not classically related to the reproductive system, such as melanoma; in melanoma cells, LHRH might act as an inhibitory factor on both cell proliferation and metastatic behavior. It is suggested that, in melanoma, LHRH receptors might represent a diagnostic marker and a possible molecular target for new therapeutic approaches for this pathology.

Stability, Permeability and Growth-Inhibitory Properties of Gonadotropin-Releasing Hormone Liposaccharides

“…LNCaP cells are derived from human androgen-sensitive prostate adenocarcinoma cells and express GnRH-R (37). Nterminal C8-modified GnRH (2, 3, 6 and 7) conjugates did not produce any significant growth inhibition in this cell line (Fig.…”

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

“…2A) (77). In melanoma-derived cells BLM and Me15392, GnRHR activation by Zoladex is able to support a high diminution in cell proliferation and matrigel invasion (70,71); in addition, in the case of leukemia, either overexpression on cell surfaces of 67-kDa LR cell surfaces or an increase in migration into bone marrow and spleen after GnRH stimulation was observed (49) ( Fig. 2A).…”

“…These include liver (63), larynx (64), pancreas (65), colon (66), lymphoma (67), kidney (68,69), skin (70,71), leukemia (49) and brain (72). The function of GnRH and GnRHR in these tumors has been associated with inhibition of proliferation in a time-and dose-related manner in respond to various molecular form of GnRH (63)(64)(65)(66)(67)(68)(69)(70)(71)(72). The response to GnRH in pancreatic tumors has been shown to be specific, it was demonstrated by the absences of binding sites for GnRH in membranes from nontumoral human pancreas tissues (65,73).…”

“…The function of these molecules in these cells remains unclear, but has been associated with cell proliferation, and migratory and invasive capacity (71,85).…”

Leuprorelin and Triptorelin in the treatment of Prostate Cancer: Medication adherence, Persistence and Economic Evaluation in Five Years of Analysis

“…In fact, approximately 90% of prostate cancer tumors respond to initial androgen deprivation, thereby improving patients' quality of life and longevity [9]. The administration of GnRH analogs, Leuprorelin and Triptorelin, is the preferred choice for the treatment of prostate cancer [10][11][12][13]. The injection of Leuprorelin or Triptorelin reduces testosterone serum level near surgically castrated [14][15][16][17].…”