engleski

The influence of Coxsackie adenovirus receptor expression on integrin expression in human embryonal rhabdomyosarcoma cell line

Coxsackie adenovirus receptor (CAR) is a component of intercellular junctions, a primary receptor for adenovirus type 5 (Ad5) and a tumor suppressor. Integrins are non-covalently associated heterodimeric cell surface adhesion molecules composed of α and β subunits that play a critical role in a number of cell functions including cell attachment, migration, growth and differentiation. Multiple types of integrin molecules that include αvβ3, αvβ5, αvβ1, α5β1 and α3β1 have been shown to act as secondary receptors for Ad5. Little is known about the influence of increased CAR expression on expression of integrins involved in Ad5 vector transduction and the information gathered so far are contradictory. The present study demonstrates that augmented CAR expression in clones of human embryonal rhabdomyosarcoma (RD) cell line leads to reduced expression of integrin subunit αv and integrin heterodimers αvβ3 and αvβ5. The aforementioned reduction was recorded on a protein level, using flow cytometry, whereas the mRNA level, measured by semiquantitative RT-PCR, did not vary in RD clones overexpressing CAR as compared to RD cells. By testing the transduction efficacy of RD cells and two RD-CAR transfectants by two recombinant Ad5s with shortened fibers, Ad5FbΔ639 and Ad5FbΔ639RGD4C, the negative effect of reduced levels of αvβ3 and αvβ5 on Ad5FbΔ639RGD4C transduction was confirmed. These findings are important for understanding the biological function of CAR. They reveal that increased expression of CAR reduces integrin αvβ3 and αvβ5 expression, which may have serious effects on adhesion, mobility and/or metastatic potential of cells, but also on the transduction efficacy of adenoviral vectors.

Coxsackie adenovirus receptor ; integrins ; transduction efficacy

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