NG2-PG in tumor vascularization and progression

NG2-PG 在肿瘤血管化和进展中的作用

• 批准号: 6622932
• 负责人: William B. Stallcup
• 金额: $ 51.7万
• 依托单位: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6622932
• 关键词: angiogenesis; breast neoplasms; cell cell interaction; cell communication molecule; cell line; genetically modified animals; laboratory mouse; lung neoplasms; melanoma; metastasis; mixed tissue /cell culture; neoplasm /cancer blood supply; neoplastic process; pancreas neoplasms; proteoglycan

DESCRIPTION: (provided by applicant) The NG2 proteoglycan is expressed by mural cells in both normal and pathological vasculature. NG2 is also expressed by many types of tumor cells. NG2 could therefore affect tumor growth and metastasis both by altering the intrinsic properties of tumor cells and by regulating tumor vascularization. Evidence exists for each of these possibilities. For example, NG2 expression by melanoma cells enhances their rate of proliferation, weakens their attachment to certain substrata, and promotes de-differentiation, resulting in faster tumor growth and enhanced metastasis. In the case of vascularization, NG2 expression by vascular mural cells appears to be required for the timely development of both macro- and microvascular structures, as evidenced by the finding that the NG2 knockout mouse exhibits delayed vascular morphcgenesis both pre- and postnatally. Since efficient vascularization is required for both tumor growth and metastasis, vascular NG2 could be a factor in regulating these aspects of tumor progression. This proposal will examine the role of both vascular and tumor cell NG2 in the vascularization and progression of tumors. Aim 1 will investigate the role of pericyte NG2 in the de novo development of breast and pancreatic tumors in MMTVIPyMT and RIP-tag transgenic mice, respectively. Introduction of these phenotypes onto the NG2 null background of NG2 knockout mice will allow assessment of the contribution of vascular NG2 to tumor progression. Aim 2 will evaluate the role of tumor cell NG2 in tumor progression. Comparison of NG2-positive and NG2-negative versions of the B 16 melanoma and the Lewis lung carcinoma will reveal NG2-dependent components of tumor growth and metastasis. Aim 3 will examine the role of NG2 in endothelial cell/mural cell communication. Co-culturing vascular endothelial cells along with NG2-positive or NG2-negative mural cells will allow a determination of the contribution of NG2 to cellular cross-talk that leads to the formation of vascular tubes.

描述：（申请人提供）NG2蛋白多糖通过壁画表达 正常和病理脉管系统中的细胞。 NG2也表示为 许多类型的肿瘤细胞。因此，NG2 可能会影响肿瘤生长并 通过改变肿瘤细胞的内在特性和通过 调节肿瘤血管化。这些都有证据存在 的可能性。例如，黑色素瘤细胞表达 NG2 可增强其 增殖率，削弱它们对某些基质的附着，并且 促进去分化，导致更快的肿瘤生长并增强 转移。在血管化的情况下，血管壁上NG2的表达 细胞似乎对于宏观和微观的及时发展是必需的。 NG2 敲除的发现证明了微血管结构 小鼠在出生前和出生后均表现出延迟的血管形态发生。自从 肿瘤生长和转移都需要有效的血管化， 血管NG2可能是调节肿瘤这些方面的一个因素 进展。 该提案将研究血管细胞和肿瘤细胞 NG2 在 肿瘤的血管化和进展。目标 1 将调查的作用 周细胞NG2在乳腺和胰腺肿瘤从头发育中的作用 分别为 MMTVIPyMT 和 RIP 标签转基因小鼠。这些的介绍 NG2 敲除小鼠的 NG2 无效背景上的表型将允许 评估血管 NG2 对肿瘤进展的贡献。目标2将 评估肿瘤细胞NG2在肿瘤进展中的作用。比较 B 16 黑色素瘤和 Lewis 肺的 NG2 阳性和 NG2 阴性版本 癌症将揭示肿瘤生长和转移的 NG2 依赖性成分。 目标 3 将检查 NG2 在内皮细胞/壁细胞中的作用 沟通。血管内皮细胞与 NG2 阳性细胞共培养 或 NG2 阴性壁细胞将允许确定 NG2 与导致血管形成的细胞串扰有关。