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

作者：Barbosa Chaves Karen Cristina; Turaca Lauro Thiago; Pesquero Joao Bosco; Mennecier Gregory; Zaidan Dagli Maria Lucia; Chammas Roger; Schor Nestor; Bellini Maria Helena^*

来源：Biomedicine & Pharmacotherapy, 2012, 66(6): 464-468.

DOI：10.1016/j.biopha.2012.04.003

• RCC
• Endostatin
• Orthotopic metastatic model
• Fibronectin

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.

• 出版日期2012-9