Fibronectin Extracellular Matix Assembly by Human Epidermal Cells Implanted Into Athymic Mice

Abstract

Human epidermal keratinocytes reorganize into epidermal inclusion cysts when implanted subcutaneously into athymic mice. During the organization and maturation of these cysts, fibronectin accumulates in the surrounding extracellular matrix and the basement membrane proteins bullous pemphigoid antigen and laminin appear at the epithelial-stromal interface. The sequence in which these proteins appear parallels that seen during reepithelialization of a skin wound in vivo. Fibronectin appears during aggregation of the epidermal cells and persists in the area surrounding the cysts for at least 7 days. Bullous pemphigoid antigen and laminin appear later (by 4 and 7 days, respectively) and ultimately become organized into a continuous band at the periphery of the cyst. This distribution of bullous pemphigoid antigen and laminin at the stromal-epithelial interface persists at least 5 weeks, suggesting that the implanted epidermal cells are capable of developing and maintaining a stable basement membrane zone. Fibronectin, which is abundant in the matrix adjacent to the epidermal cysts and in the surrounding stroma during cyst organization and maturation, diminishes to undetectable levels by 5 weeks. While much of the fibronectin derives from the host tissues, species-specific antibodies to human fibronectin reveal that at least a portion of this protein is synthesized and deposited by the implanted epidermal cells.