Open AccessInhibition of tumor‐induced edema by antisense VEGF is mediated by suppressive vesiculo‐vacuolar organelles (VVO) formation
Author(s) -
Lin Zhi Xiong,
Yang Li Juan,
Huang Qian,
Lin Jian Hua,
Ren Jie,
Chen Zhen Bin,
Zhou Lin Ying,
Zhang Peng Fei,
Fu Jin
Publication year - 2008
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2008.00974.x
Subject(s) - angiogenesis , vascular permeability , vascular endothelial growth factor , cancer research , edema , microbiology and biotechnology , glioma , transfection , biology , pathology , chemistry , medicine , cell culture , vegf receptors , genetics
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. ( Cancer Sci 2008; 99: 2540–2546)