Increased expression of the coxsackie and adenovirus receptor downregulates αvβ3 and αvβ5 integrin expression and reduces cell adhesion and migration

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• 作者：Dragomira Majhen^a ; Nikolina Stojanović ; ^a ; Tea Š ; peljko¹ ; ^a ; Anamaria Brozovic^a ; Tihana De Zan^a ; Maja Osmak^a ; Andreja Ambriović ; -Ristov ; ^a ; ^{andrea@irb.hr"" rel=""nofollow}
• 关键词：Coxsackie and adenovirus receptor ; &#x3b1 ; vβ ; 3 integrin ; &#x3b1 ; vβ ; 5 integrin ; Adhesion ; Migration ; Adenovirus type 5 transduction ; Rhabdomyosarcoma
• 刊名：Life Sciences
• 出版年：2011
• 出版时间：15 August 2011
• 年：2011
• 卷：89
• 期：7-8
• 页码：241-249
• 全文大小：1437 K

文摘

Aims

Coxsackie and adenovirus receptor (CAR) is a tumor suppressor and a primary receptor for adenovirus type 5 (Ad5). Our study aims to examine the influence of forced expression of CAR in rhabdomyosarcoma cells (RD) on expression levels of integrins implicated in Ad5 entry, and the effect of CAR on cell–extracellular matrix adhesion and migration.

Main methods

CAR expressing clones were established from RD cells by stable transfection. Flow cytometry was used to evaluate the expression of CAR and integrins. Adhesion was measured in plates previously coated with vitronectin or fibronectin. Boyden chambers were used to investigate migration. Transfection of cells with siRNA was used to achieve integrin silencing. Ad5-mediated transgene expression was measured by β-gal staining.

Key findings

Increased expression of CAR in RD cells reduces the expression of αvβ3 and αvβ5 integrins. Cells overexpressing CAR exhibit significantly reduced adhesion to vitronectin and fibronectin, and reduced cell migration. Specifically silencing αvβ3 integrin in RD cells reduced cell migration indicating that reduced migration could be the consequence of αvβ3 integrin downregulation. This study also demonstrates the negative effect of reduced levels of αvβ3 and αvβ5 integrins on Ad5-mediated transgene expression with Ad5 retargeted to αv integrins.

Significance

The pharmacological upregulation of CAR aimed to increase Ad5-mediated transgene expression may actually downregulate αvβ3 and αvβ5 integrins and thus alter Ad5-mediated gene transfer. The mechanism of decreased cell migration, a prerequisite for metastasis and invasion, due to increased CAR expression may be explained by reduced αvβ3 integrin expression.