Inhibition of tumor-induced edema by antisense VEGF is mediated by suppressive vesiculo-vacuolar organelles (VVO) formation.
Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis, vasculogenesis and vascular permeability. Edema in glioma tumors is considered one of the most pathological characteristics, but the mechanism of regulating vascular permeability is still unclear. In the present study, tumorigenic mice were generated by subcutaneous injection of glioma cell lines, C6-null cells and stable transfected-C6 cells overexpressing mock vector (C6-mock) and antisense VEGF (C6-VEGF(-/-)). Overexpression of antisense VEGF (C6-VEGF(-/-) mice) significantly suppressed tumor growth, decreased angiogenesis and reduced tumoral edema. Further studies by electron microscope revealed that tumor-induced hyperpermeability was mediated by formation of vesiculo-vacuolar organelles (VVO), specifically reducing the number of vesicle and caveolae in VVO, and this effect was blocked, at least partially, by antisense VEGF. These data show a possible mechanism of tumor-induced hyperpermeability and indicate that blockage of VEGF might contribute to therapeutical strategies for tumor edema.
Lin
Zhi Xiong
ZX
Dept of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou 35005, China. lzx@mail.fjmu.edu.cn
Yang
Li Juan
LJ
Huang
Qian
Q
Lin
Jian Hua
JH
Ren
Jie
J
Chen
Zhen Bin
ZB
Zhou
Lin Ying
LY
Zhang
Peng Fei
PF
Fu
Jin
J
D000818:Animals; D000831:Animals, Newborn; D016375:Antisense Elements (Genetics) / Q000235:genetics; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000096:biosynthesis; D004487:Edema / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015316:Genetic Therapy / Q000379:methods; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D015388:Organelles / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D010957:Plasmids; D051381:Rats; D017207:Rats, Sprague-Dawley; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D014162:Transfection; D014617:Vacuoles / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D016375:Antisense Elements (Genetics); D018076:DNA, Complementary; D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor