Pericyte deficiencies lead to aberrant tumor vascularizaton in the brain of the NG2 null mouse.
Tightly regulated crosstalk between endothelial cells and pericytes is required for formation and maintenance of functional blood vessels. When the NG2 proteoglycan is absent from pericyte surfaces, vascularization of syngeneic tumors growing in the C57Bl/6 mouse brain is aberrant in several respects, resulting in retardation of tumor progression. In the NG2 null mouse brain, pericyte investment of the tumor vascular endothelium is reduced, causing deficiencies in both pericyte and endothelial cell maturation, as well as reduced basal lamina assembly. While part of this deficit may be due to the previously-identified role of NG2 in beta1 integrin-dependent periyte/endothelial cell crosstalk, the ablation of NG2 also appears responsible for loss of collagen VI anchorage, in turn leading to reduced collagen IV deposition. Poor functionality of tumor vessels in NG2 null brain is reflected by reduced vessel patency and increased vessel leakiness, resulting in large increases in tumor hypoxia. These findings demonstrate the importance of NG2-dependent pericyte/endothelial cell interaction in the development and maturation of tumor blood vessels, identifying NG2 as a potential target for anti-angiogenic cancer therapy.
Huang
Feng-Ju
FJ
Sanford-Burnham Medical Research Institute, Cancer Center, La Jolla, CA 92037, USA.
You
Weon-Kyoo
WK
Bonaldo
Paolo
P
Seyfried
Thomas N
TN
Pasquale
Elena B
EB
Stallcup
William B
WB
D000818:Animals; D000941:Antigens; D001485:Basement Membrane / Q000473:pathology / Q000503:physiopathology; D001808:Blood Vessels / Q000254:growth & development / Q000473:pathology / Q000503:physiopathology; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002450:Cell Communication; D002454:Cell Differentiation; D042783:Endothelial Cells / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D005109:Extracellular Matrix / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000473:pathology* / Q000503:physiopathology; D020286:Pericytes / Q000473:pathology; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4