Evaluation of Hedgehog Signaling in Myogenic Sarcomas

肌源性肉瘤中 Hedgehog 信号转导的评估

• 批准号: 6999108
• 负责人: JOHN J LEE
• 金额: $ 3.75万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-16 至 2006-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6999108
• 关键词: athymic mouse; biological signal transduction; cell line; molecular oncology; muscle neoplasms; neoplastic cell; neoplastic growth; postdoctoral investigator; rhabdomyosarcoma

DESCRIPTION (provided by applicant): The Hedgehog signaling pathway has recently been implicated in the formation of multiple tumor types in humans and vertebrate animals. One of these tumor types is rhabdomyosarcoma, an aggressive soft-tissue sarcoma histologically related to skeletal muscle. In this proposal we will investigate the mechanisms through which Hedgehog pathway activation causes growth of rhabdomyosarcomas and other myogenic sarcomas. Our initial aim will be to phenotypically identify and isolate tumor stem cells from primary rhabdomyosarcoma cell lines which require Hedgehog pathway activity for growth. We will also survey a variety of primary human and mouse myogenic sarcoma cell lines to determine if the Hedgehog pathway is universally necessary for driving tumor growth. In this survey we will simultaneously determine if other well known tumor-growth driving signaling pathways, specifically Wnt and Notch, have a role in the proliferation of myogenic sarcoma cells. Finally, we will see if the growth driving signaling pathways identified for myogenic sarcomas contribute to the maintenance and/or proliferation of a tumor specific stem-cell population.

描述（由申请人提供）：Hedgehog 信号通路最近与人类和脊椎动物多种肿瘤类型的形成有关。其中一种肿瘤类型是横纹肌肉瘤，一种组织学上与骨骼肌相关的侵袭性软组织肉瘤。在本提案中，我们将研究 Hedgehog 通路激活导致横纹肌肉瘤和其他肌源性肉瘤生长的机制。我们的最初目标是从表型上鉴定并从需要 Hedgehog 通路活性才能生长的原代横纹肌肉瘤细胞系中分离肿瘤干细胞。我们还将调查各种原代人类和小鼠肌源性肉瘤细胞系，以确定 Hedgehog 通路是否普遍需要驱动肿瘤生长。在这项调查中，我们将同时确定其他众所周知的肿瘤生长驱动信号通路，特别是 Wnt 和 Notch，是否在肌源性肉瘤细胞的增殖中发挥作用。最后，我们将了解针对肌源性肉瘤确定的生长驱动信号通路是否有助于肿瘤特异性干细胞群的维持和/或增殖。