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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA095287-04
Application #
6881044
Study Section
Pathology B Study Section (PTHB)
Program Officer
Sussman, Daniel J
Project Start
2002-04-01
Project End
2007-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
4
Fiscal Year
2005
Total Cost
$440,550
Indirect Cost
Name
Sanford-Burnham Medical Research Institute
Department
Type
DUNS #
020520466
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Tang, Fengying; Lord, Megan S; Stallcup, William B et al. (2018) Cell surface chondroitin sulphate proteoglycan 4 (CSPG4) binds to the basement membrane heparan sulphate proteoglycan, perlecan, and is involved in cell adhesion. J Biochem 163:399-412
You, Weon-Kyoo; Stallcup, William B (2017) Localization of VEGF to Vascular ECM Is an Important Aspect of Tumor Angiogenesis. Cancers (Basel) 9:
Stallcup, William B (2017) NG2 Proteoglycan Enhances Brain Tumor Progression by Promoting Beta-1 Integrin Activation in both Cis and Trans Orientations. Cancers (Basel) 9:
Guimarães-Camboa, Nuno; Cattaneo, Paola; Sun, Yunfu et al. (2017) Pericytes of Multiple Organs Do Not Behave as Mesenchymal Stem Cells In Vivo. Cell Stem Cell 20:345-359.e5
Xavier, Sandhya; Sahu, Ranjit K; Landes, Susan G et al. (2017) Pericytes and immune cells contribute to complement activation in tubulointerstitial fibrosis. Am J Physiol Renal Physiol 312:F516-F532
Tao, Liang; Zhang, Jie; Meraner, Paul et al. (2016) Frizzled proteins are colonic epithelial receptors for C. difficile toxin B. Nature 538:350-355
Stallcup, William B; You, Weon-Kyoo; Kucharova, Karolina et al. (2016) NG2 Proteoglycan-Dependent Contributions of Pericytes and Macrophages to Brain Tumor Vascularization and Progression. Microcirculation 23:122-33
Cejudo-Martin, Pilar; Kucharova, Karolina; Stallcup, William B (2016) Role of NG2 proteoglycan in macrophage recruitment to brain tumors and sites of CNS demyelination. Trends Cell Mol Biol 11:55-65
Liu, Xiangyou; Braun, Gary B; Zhong, Haizheng et al. (2016) Tumor-Targeted Multimodal Optical Imaging with Versatile Cadmium-Free Quantum Dots. Adv Funct Mater 26:267-276
She, Zhi-Gang; Chang, Yunchao; Pang, Hong-Bo et al. (2016) NG2 Proteoglycan Ablation Reduces Foam Cell Formation and Atherogenesis via Decreased Low-Density Lipoprotein Retention by Synthetic Smooth Muscle Cells. Arterioscler Thromb Vasc Biol 36:49-59

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