NG2-PG in tumor vascularization and progression

描述：(申请人提供)NG2蛋白多糖通过壁画表达 正常和病理性血管中的细胞。NG2也表示为 多种类型的肿瘤细胞。因此NG2可能会影响肿瘤的生长和 通过改变肿瘤细胞的固有属性和通过 调节肿瘤血管生成。所有这些都有证据支持 可能性。例如，黑色素瘤细胞NG2的表达增强了它们的 增殖率，削弱了它们对某些底物的附着，以及 促进去分化，导致肿瘤更快生长和增强 转移。在血管化的情况下，血管壁上NG2的表达 细胞似乎是及时发展宏观和 微血管结构，如发现NG2基因敲除 小鼠出生前和出生后都表现出血管形态发生的延迟。自.以来 肿瘤的生长和转移都需要有效的血管形成， 血管NG2可能是调节肿瘤这些方面的一个因素 进步。 这项建议将研究血管和肿瘤细胞NG2在 肿瘤的血管形成和进展。目标1将调查 周细胞NG2在小鼠乳腺和胰腺肿瘤新生发展中的作用 MMTVIPyMT和RIP-Tag转基因小鼠。介绍这些产品 NG2基因敲除小鼠NG2缺失背景的表型将允许 评估血管NG2在肿瘤进展中的作用。目标2将 评估肿瘤细胞NG2在肿瘤进展中的作用。比较 B16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依赖成分。 目标3将研究NG2在内皮细胞/壁细胞中的作用 沟通。与NG2阳性的血管内皮细胞共培养 或NG2阴性的壁细胞将允许确定 NG2与导致血管形成的细胞串扰有关。

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.