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.

原发性CNS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）已被证明影响生长， 在许多外周组织中的发育和分化， 胎脑星形胶质细胞和神经元细胞的原代培养物。 的 IGFs及其结合蛋白的内源性产生，以及 大脑中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，IGFs已被证明是通过内分泌、自分泌 或旁分泌途径在几个人的生长调节 恶性肿瘤（3-5）。 我们最近报道IGF-II是一种 自分泌生长因子的人横纹肌肉瘤，是一种自分泌 和/或用于神经母细胞瘤的旁分泌生长因子（4-5）。 最近的研究 已经鉴定了IGF受体和IGF-I的特异性mRNA的存在 和II在一些人类脑肿瘤中（6，7）。 因此，我们假设 IGFs在人脑的生长调节中起着积极的作用 恶性肿瘤。 我们最近报道了IGF-II刺激人类细胞运动， 横纹肌肉瘤9例。 恶性神经胶质瘤和髓母细胞瘤是 以高度的局部侵袭性为特征。 由于肿瘤 入侵需要主动运动，我们假设IGFs在这一过程中起着关键作用。 在调节肿瘤细胞运动和侵袭中的作用。 我们 推测这些功能可能由II型受体介导， 类似于我们在横纹肌肉瘤中所示（9）。 因此，我们将描述IGF，IGF受体和IGF结合 人类脑肿瘤细胞中的蛋白质，并分析它们与 肿瘤生长、运动和侵袭。