INSULIN-LIKE GROWTH FACTORS IN GROWTH, INVASIVENESS AND MOTILITY OF BRAIN TUMORS

脑肿瘤生长、侵袭性和运动性中的胰岛素样生长因子

• 批准号: 3751879
• 负责人: CATERINA MINNITI
• 金额: --
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3751879
• 关键词: biological signal transduction; cell cycle; cell growth regulation; cell motility; glioblastoma multiforme; growth factor receptors; human tissue; in situ hybridization; insulinlike growth factor; medulloblastoma; neoplasm /cancer invasiveness; northern blottings; receptor binding; tissue /cell culture; transport proteins

Primary CNS neoplasms account for 20% of all pediatric malignancies and are the most common solid tumors in children. Insulin-like growth factor I and II (IGF-I and IGF-II) have been demonstrated to influence growth, development and differentiation in numerous peripheral tissues and in primary cultures of astroglial and neuronal cells from fetal brain. The endogenous production of IGFs and their binding proteins as well as the presence of IGF receptors in the brain suggests that these peptides may regulate proliferation, development and differentiation of brain cells (1,2). In addition, IGFs have been shown to act by endocrine, autocrine or paracrine pathways in the growth regulation of several human malignancies (3-5). We have recently reported that IGF-II is an autocrine growth factor for human rhabdomyosarcomas, and is an autocrine and/or paracrine growth factor for neuroblastomas (4-5). Recent studies have identified the presence of IGF receptors and specific mRNA for IGF-I and II in some human brain tumors (6,7). Therefore, we hypothesize that IGFs play an active role in the growth regulation of human brain malignancies. We recently reported that IGF-II stimulates cell motility in human rhabdomyosarcomas (9). Malignant gliomas and medulloblastomas are characterized by a high degree of local invasiveness. Since tumor invasion requires active locomotion, we hypothesize that IGFs play a key role in modulating tumor cell locomotion and, hence, invasion. We speculate that these functions may be mediated by the type II receptor, in analogy to what we have shown in rhabdomyosarcoma (9). Therefore, we will characterize IGFs, IGF receptors, and IGF binding proteins in human brain tumor cells and analyze their relationship to tumor growth, motility, and invasion.

主要中枢神经系统肿瘤占所有儿科恶性肿瘤的20％ 是儿童中最常见的实体瘤。 胰岛素样生长因子 I和II（IGF-I和IGF-II）已被证明会影响生长， 众多周围组织的发展和分化 来自胎儿大脑的星形胶质细胞和神经元细胞的一级培养。 这 IGF的内源性产生及其结合蛋白以及 大脑中的IGF受体的存在表明这些肽可能 调节脑细胞的增殖，发育和分化 （1,2）。 此外，IGF已被表明由内分泌生殖器作用 或几个人的生长调节中的旁分泌途径 恶性肿瘤（3-5）。 我们最近报告说IGF-II是 人类横纹肌肉瘤的自分泌生长因子，是自分泌 神经母细胞瘤的旁分泌生长因子（4-5）。 最近的研究 已经确定了IGF受体的存在和IGF-I的特异性mRNA 和II在某些人脑肿瘤中（6,7）。 因此，我们假设 IGF在人脑的生长调节中起积极作用 恶性肿瘤。 我们最近报道，IGF-II刺激了人类的细胞运动 横纹肌肉瘤（9）。 恶性神经胶质瘤和髓母细胞瘤是 以高度的局部侵入性为特征。 由于肿瘤 入侵需要主动运动，我们假设IGF播放钥匙 在调节肿瘤细胞运动和入侵中的作用。 我们 推测这些功能可能是由II型受体介导的， 类似于我们在横纹肌肉瘤中所显示的内容（9）。 因此，我们将表征IGF，IGF受体和IGF结合 人脑肿瘤细胞中的蛋白质并分析其与 肿瘤生长，运动和入侵。