NG2-PG in tumor vascularization and progression

描述：（由申请人提供）NG 2蛋白聚糖由壁表达 正常和病理性脉管系统中的细胞。NG 2也表示为 多种类型的肿瘤细胞因此，NG 2可以影响肿瘤生长， 通过改变肿瘤细胞的内在特性和通过 调节肿瘤血管形成。每一种都有证据 可能性例如，黑色素瘤细胞的NG 2表达增强了它们的免疫应答。 增殖速度，削弱它们对某些基质的附着， 促进去分化，导致肿瘤生长更快， 转移在血管化的情况下，血管壁NG 2表达 细胞似乎需要及时发展的宏观和 微血管结构，这一发现证明，NG 2敲除 小鼠在出生前和出生后均表现出延迟的血管形态发生。以来 肿瘤生长和转移都需要有效的血管形成， 血管NG 2可能是调节肿瘤这些方面的一个因子 进展 该建议将研究血管和肿瘤细胞NG 2在肿瘤发生中的作用。 血管化和肿瘤进展。目标1将研究 周细胞NG 2在乳腺和胰腺肿瘤的新生发展中的作用 MMTVIPyMT和RIP-标签转基因小鼠。引入这些 将表型转移到NG 2敲除小鼠的NG 2无效背景上将允许 评估血管NG 2对肿瘤进展的贡献。目标2将 评价肿瘤细胞NG 2在肿瘤进展中的作用。比较 NG 2阳性和NG 2阴性的B 16黑色素瘤和刘易斯肺 癌症将揭示肿瘤生长和转移的NG 2依赖性组分。 目的3：研究NG 2在内皮细胞/壁细胞中的作用。 通信血管内皮细胞沿着与NG 2阳性细胞共培养 或NG 2阴性的壁细胞将允许确定 NG 2的细胞串扰，导致血管的形成。

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.