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Expression and Functional Analysis of Tumor-Related Factor S100A4 in Antler Stem Cells

Annual antler renewal is a stem cell–based epimorphic process driven by antler stem cells (ASCs) resident in antlerogenic periosteum (AP). Antlerogenic periosteal cells express a high level of S100A4, a metastasis-associated protein, which intrigued us to explore what role S100A4 could play in antler regeneration. The present study set out to investigate expression and effects of S100A4 in the ASCs and their progeny. The results showed that not only did cells from the AP express a high level of S100A4, but also the pedicle periosteum and the antler growth center. In the antler growth center, we found S100A4-positive cells were specifically located in blood vessel walls and in vascularized areas. In vitro, recombinant deer S100A4 protein stimulated the proliferation of the AP cells, promoted proliferation, migration and tube formation of human vascular endothelial cells, and enhanced migration of Hela cells, but not AP cells. These findings demonstrated that S100A4 in the ASCs may play a significant role in stimulating angiogenesis, proliferation, but not motility, of ASCs. Deer antlers offer a unique model to explore how rapid cell proliferation with a high level of S100A4 expression is elegantly regulated without becoming cancerous.