Differential Regulation of a Fibroblast Growth Factor-Binding Protein during Skin Carcinogenesis and Wound Healing1

• Published in: Neoplasia (New York, N.Y.) Vol. 6; no. 5; pp. 595 - 602
• Main Authors: Kurtz, Andreas, Aigner, Achim, Cabal-Manzano, Rafael H, Butler, Robert E, Hood, Dozier R, Sessions, Roy B, Czubayko, Frank, Wellstein, Anton
• Format: Journal Article
• Language: English
• Published: Neoplasia Press Inc 01.09.2004
• ISSN: 1522-8002; 1476-5586

The initiation of premalignant lesions is associated with subtle cellular and gene expression changes. Here we describe a severe combined immunodeficient mouse xenograft model with human adult skin and compare chemical carcinogenesis and wound healing. We focus on a secreted binding protein for fibroblast growth factors (FGF-BP) that enhances the activity of locally stored FGFs and is expressed at high levels in human epithelial cancers. Carcinogen treatment of murine skin induced papilloma within 6 weeks, whereas the human skin grafts displayed no obvious macroscopic alterations. Microscopic studies of the human skin, however, showed p53 -positive keratinocytes in the epidermis, increased angiogenesis in the dermis of the treated skin, enhanced proliferation of keratinocytes in the basal layer, and an increase of FGF-BP protein and mRNA expression. In contrast, after surgical wounding of human skin grafts or of mouse skin, FGF-BP expression was upregulated within a few hours and returned to control levels after 2 days with wound closure. Enhanced motility of cultured keratinocytes and dermal fibroblasts by FGF-BP supports a role in wound healing. We conclude that adult human skin xenografts can be used to identify early molecular events during malignant transformation as well as transient changes during wound healing.