Functional characterization of Gonadotropin Releasing Hormone Receptor (GnRH-R) in Non Hodgkin´s Lymphoma (NHL) and Urothelial Carcinoma- a novel therapeutic target

促性腺激素释放激素受体 (GnRH-R) 在非霍奇金淋巴瘤 (NHL) 和尿路上皮癌中的功能特征 - 一种新的治疗靶点

• 批准号: 229001970
• 负责人: Professorin Dr. Gunhild von Amsberg
• 金额: --
• 依托单位: Institut für Pathologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2012
• 资助国家: 德国
• 起止时间: 2011-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/229001970?language=en
• 关键词: Functional; characterization; Gonadotropin; Releasing; Hormone

The expression of the Gonadotropin Releasing Hormone Receptor (GnRH-R) is mostly limited to the pituitary gland and the reproductive organs. Remarkably, GnRH-R can be detected in tumors which originate from GnRH-R negative tissues. Thus, GnRH-R is a promising loop whole for targeted therapy. The role of GnRH-R in malignant development and spreading of non hodgkin´s lymphoma (NHL) and urothelial carcinoma has not been determined yet. Therefore, functional characterization of GnRH-R shall be carried out in these malignancies. The influence of GnRH-R activity on subcellular calcium homeostasis, signal transduction pathways as well as on cell migration and invasion is to be examined. Overexpression by transfection shall clarify the influence of GnRH-R on malignant transformation. Furthermore, the impact of a potential interaction between GnRH-R and Epidermal Growth Factor Receptor is to be investigated in urothelial carcinoma. A comparison with EGFR negative NHL allows to find differences and common structures in signal transduction. The therapeutic potential of GnRH-R will be evaluated by receptor stimulation, inhibition and treatment with cytotoxic GnRH-analogs. Parallel and serial combination therapies of GnRH analogs with EGFR inhibitors are of particular interest in order to overcome primary or secondary resistance.

促性腺激素释放激素受体(GnRH-R)的表达主要局限于脑下垂体和生殖器官。值得注意的是，在来自GnRH-R阴性组织的肿瘤中可以检测到GnRH-R。因此，GnRH-R是一个有希望的靶向治疗循环整体。促性腺激素释放激素受体在非霍奇金S淋巴瘤和尿路上皮癌恶性发展和扩散中的作用尚未确定。因此，应在这些恶性肿瘤中进行GnRH-R的功能鉴定。GnRH-R活性对亚细胞钙稳态、信号转导途径以及细胞迁移和侵袭的影响有待研究。GnRH-R的过表达有助于阐明GnRH-R在细胞恶性转化过程中的作用。此外，GnRH-R和表皮生长因子受体之间的潜在相互作用对尿路上皮癌的影响还有待研究。与EGFR阴性的非霍奇金淋巴瘤进行比较，可以发现信号转导的不同和共同结构。GnRH-R的治疗潜力将通过受体的刺激、抑制和细胞毒性GnRH类似物的治疗来评估。GnRH类似物与EGFR抑制剂的并行和串联联合治疗对于克服原发或继发耐药特别有意义。