Perivascular nitric oxide gradients normalize tumor vasculature.
Normalization of tumor vasculature is an emerging strategy to improve cytotoxic therapies. Here we show that eliminating nitric oxide (NO) production from tumor cells via neuronal NO synthase silencing or inhibition establishes perivascular gradients of NO in human glioma xenografts in mice and normalizes the tumor vasculature, resulting in improved tumor oxygenation and response to radiation treatment. Creation of perivascular NO gradients may be an effective strategy for normalizing abnormal vasculature.
Kashiwagi
Satoshi
S
Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 100 Blossom Street, Boston, Massachusetts 02114, USA.
Tsukada
Kosuke
K
Xu
Lei
L
Miyazaki
Junichi
J
Kozin
Sergey V
SV
Tyrrell
James A
JA
Sessa
William C
WC
Gerweck
Leo E
LE
Jain
Rakesh K
RK
Fukumura
Dai
D
D000818:Animals; D045744:Cell Line, Tumor; D020868:Gene Silencing; D005910:Glioma / Q000098:blood supply* / Q000378:metabolism* / Q000532:radiotherapy; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000201:enzymology / Q000378:metabolism / Q000532:radiotherapy; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism
D018398:Homeodomain Proteins; C064658:RAG-1 protein; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D010100:Oxygen