BACKGROUND: Capsular contracture is a devastating complication of postmastectomy implant-based breast reconstruction. Unfortunately, capsular contracture rates are drastically increased by targeted radiotherapy, a standard postmastectomy 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: The authors analyzed Thy1 expression in primary human capsular tissue and primary fibroblast explants by real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemistry. Thy1 was depleted using RNA interference to determine whether Thy1 expression was essential for the myofibroblast phenotype in capsular fibroblasts. Furthermore, human capsular fibroblasts were treated with a new antiscarring compound, salinomycin, to determine whether Thy1 expression and myofibroblast formation were blocked by salinomycin. RESULTS: In this article, the authors show that radiation therapy significantly increased Thy1 mRNA and protein expression in periimplant 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. Depletion of Thy1 decreased the fibrotic morphology of capsular fibroblasts and significantly decreased α-smooth muscle actin and collagen levels. Furthermore, the authors 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 overexpression may contribute to increased capsular contracture severity, and fibroblast scar production can be ameliorated through targeting Thy1 expression. Importantly, the authors' new results show promise for the antiscarring ability of salinomycin in radiation-induced capsular contracture. CLINCAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.
BACKGROUND: Capsular contracture is a devastating complication of postmastectomy implant-based breast reconstruction. Unfortunately, capsular contracture rates are drastically increased by targeted radiotherapy, a standard postmastectomy 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: The authors analyzed Thy1 expression in primary human capsular tissue and primary fibroblast explants by real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemistry. Thy1 was depleted using RNA interference to determine whether Thy1 expression was essential for the myofibroblast phenotype in capsular fibroblasts. Furthermore, human capsular fibroblasts were treated with a new antiscarring compound, salinomycin, to determine whether Thy1 expression and myofibroblast formation were blocked by salinomycin. RESULTS: In this article, the authors show that radiation therapy significantly increased Thy1 mRNA and protein expression in periimplant 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. Depletion of Thy1 decreased the fibrotic morphology of capsular fibroblasts and significantly decreased α-smooth muscle actin and collagen levels. Furthermore, the authors 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 overexpression may contribute to increased capsular contracture severity, and fibroblast scar production can be ameliorated through targeting Thy1 expression. Importantly, the authors' new results show promise for the antiscarring ability of salinomycin in radiation-induced capsular contracture. CLINCAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.
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