Fibronectin expression is decreased in metastatic renal cell carcinoma following endostatin gene therapy

被引：11

作者：

Barbosa Chaves, Karen Cristina ^{[1
]}

Turaca, Lauro Thiago ^{[2
]}

Pesquero, Joao Bosco ^{[2
]}

Mennecier, Gregory ^{[3
]}

Zaidan Dagli, Maria Lucia ^{[3
]}

Chammas, Roger ^{[4
]}

Schor, Nestor ^{[1
]}

Bellini, Maria Helena ^{[1
,5
]}

机构：

[1] Univ Fed Sao Paulo, Dept Med, Div Nephrol, Sao Paulo, Brazil

[2] Univ Fed Sao Paulo, Dept Biophys, Sao Paulo, Brazil

[3] Univ Sao Paulo, Sch Vet Med & Anim Sci, Dept Pathol, Sao Paulo, Brazil

[4] Univ Sao Paulo, Dept Radiol, Sao Paulo, Brazil

[5] Univ Sao Paulo, IPEN CNEN, Dept Biotechnol, Sao Paulo, Brazil

来源：

BIOMEDICINE & PHARMACOTHERAPY | 2012年 / 66卷 / 06期

基金：

巴西圣保罗研究基金会;

关键词：

RCC; Endostatin; Orthotopic metastatic model; Fibronectin; HUMAN ENDOTHELIAL-CELLS; TARGETED THERAPIES; CANCER; ACTIVATION; INTEGRINS; PATHWAY; GROWTH; MICE;

D O I：

10.1016/j.biopha.2012.04.003

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Tumor cells induce the disruption of homeostasis between cellular and extracellular compartments to favor tumor progression. The expression of fibronectin (FN), a matrix glycoprotein, is increased in several carcinoma cell types, including renal cell carcinoma (RCC). RCC are highly vascularized tumors and are often amenable to antiangiogenic therapy. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we examined the modulation of FN gene expression by ES gene therapy in a murine metastatic renal cell carcinoma (mRCC) model. Balb/C mice bearing Renca cells were treated with NIH/3T3-LXSN cells or NIH/3T3-LendSN cells. At the end of the experiment, the ES serum levels were measured, and the FN gene expression was assessed using real-time PCR. The tissue FN was evaluated by western blotting and by immunofluorescence analysis. The ES serum levels in treated mice were higher than those in the control group (P < 0.05). ES treatment led to significant decreases at the FN mRNA (P < 0.001) and protein levels (P < 0.01). Here, we demonstrate the ES antitumor effect that is mediated by down-regulation of FN expression in mRCC. (C) 2012 Elsevier Masson SAS. All rights reserved.

引用

页码：464 / 468

页数：5