| RRC ID |
42711
|
| 著者 |
Browne M, Stellmach V, Cornwell M, Chung C, Doll JA, Lee EJ, Jameson JL, Reynolds M, Superina RA, Abramson LP, Crawford SE.
|
| タイトル |
Gene transfer of pigment epithelium-derived factor suppresses tumor growth and angiogenesis in a hepatoblastoma xenograft model.
|
| ジャーナル |
Pediatr Res
|
| Abstract |
Normal hepatocytes express pigment epithelium-derived factor (PEDF), an endogenous antiangiogenic factor. We hypothesized that decreased PEDF expression may be one mechanism driving hepatoblastoma growth, and in vivo gene transfer of PEDF could suppress neovascularization and limit tumor growth. PEDF functional activity was determined in vitro using endothelial cell migration assays and in vivo using a subcutaneous tumor model. HUH-6 human hepatoblastoma tumors were treated with hybrid adenoviral/adeno-associated viral expression vectors for PEDF (Hyb-PEDF, n = 4) or beta-galactosidase (Hyb-betagal, n = 4) daily for 4 d. Mitotic figures, microvascular density (MVD), PEDF, and VEGF expression were assessed. Hyb-PEDF treatment inhibited in vivo tumor growth (p < 0.008) and decreased MVD (p < 0.001), the number of mitotic figures (p < 0.001), and VEGF expression when compared with Hyb-betagal-treated tumors. HUH-6 expression of PEDF was dramatically reduced when cultured under hypoxic conditions and also when grown in vivo, and the addition of neutralizing anti-PEDF antibody increased the already high baseline angiogenic activity of the HUH-6 cell secretions in vitro (p < 0.04). PEDF is an important endogenous regulator of the liver vasculature. Augmenting intra-tumoral PEDF levels inhibits tumor growth by reducing angiogenesis and VEGF expression. Potent inhibitors of angiogenesis, such as PEDF, may be an effective alternative treatment for children with hepatoblastoma.
|
| 巻・号 |
60(3)
|
| ページ |
282-7
|
| 公開日 |
2006-9-1
|
| DOI |
10.1203/01.pdr.0000232789.86632.91
|
| PII |
01.pdr.0000232789.86632.91
|
| PMID |
16857775
|
| MeSH |
Animals
Cell Line, Tumor
Disease Models, Animal
Eye Proteins / genetics*
Eye Proteins / metabolism
Female
Genetic Therapy*
Hepatoblastoma / therapy*
Humans
Liver Neoplasms / therapy*
Mice
Neovascularization, Pathologic / therapy*
Nerve Growth Factors / genetics*
Nerve Growth Factors / metabolism
Serpins / genetics*
Serpins / metabolism
Transplantation, Heterologous
|
| IF |
2.747
|
| 引用数 |
20
|
|
WOS 分野
|
PEDIATRICS
|
| リソース情報 |
| ヒト・動物細胞 |
HuH-6(RCB1367) |
