Background
Capsular contracture is a devastating complication of post-mastectomy implant-based breast reconstruction. Unfortunately, capsular contracture rates are drastically increased by targeted radiotherapy, a standard post-mastectomy treatment. Thy1 (also called CD90) is important in myofibroblast differentiation and scar tissue formation. However, the impact of radiotherapy on Thy1 expression and the role of Thy1 in capsular contracture are unknown.
Methods
We analyzed Thy1 expression in primary human capsular tissue and primary fibroblast explants by RT-qPCR, Western blotting, and immunohistochemistry. Thy1 was depleted using RNA interference to determine if Thy1 expression was essential for the myofibroblast phenotype in capsular fibroblasts. Furthermore, human capsular fibroblasts were treated with a new anti-scarring compound, salinomycin to determine if Thy1 expression and myofibroblast formation were blocked by salinomycin.
Results
Herein, we show that radiation therapy significantly increased Thy1 mRNA and protein expression in peri-implant scar tissue. Capsular fibroblasts explanted from scar tissue retained the ability to make the myofibroblast produced scar forming components collagen I and α-smooth muscle actin (αSMA). Depletion of Thy1 decreased the fibrotic morphology of capsular fibroblasts and significantly decreased αSMA and collagen levels. Furthermore, we show for the first time that salinomycin decreased Thy1 expression and prevented myofibroblast formation in capsular fibroblasts.
Conclusions
These data reveal that ionizing radiation-induced Thy1 over-expression may contribute to increased capsular contracture severity, and fibroblast scar production can be ameliorated through targeting Thy1 expression. Importantly, our new results show promise for the anti-scarring ability of salinomycin in radiation-induced capsular contracture.