The Role of Fibroblast Growth Factor-Binding Protein 1 in Skin Carcinogenesis and Inflammation

Marcel Oliver Schmidt*, Khalid Ammar Garman, Yong Gu Lee, Chong Zuo, Patrick James Beck, Mingjun Tan, Juan Antonio Aguilar-Pimentel, Markus Ollert, Carsten Schmidt-Weber, Helmut Fuchs, Valerie Gailus-Durner, Martin Hrabe de Angelis, Lore Becker, Alexandra Vernaleken, Thomas Klopstock, Thure Adler, Irina Treise, Marion Horsch, Kristin Moreth, Robert BrommageWolfgang Hans, Manuela Östereicher, Ralph Steinkamp, Christoph Lengger, Holger Maier, Claudia Stoeger, Stefanie Leuchtenberger, Dirk H. Busch, Johannes Beckers, Raffi Bekeredjian, Lillian Garrett, Sabine M. Hölter, Annemarie Zimprich, Oana Amarie, Wolfgang Wurst, Jochen Graw, Jan Rozman, Julia Calzada-Wack, Patricia da Silva-Buttkus, Frauke Neff, Martin Klingenspor, Ildiko Racz, Andreas Zimmer, Birgit Rathkolb, Eckhard Wolf, Elena Tassi, Anna Tate Riegel, Anton Wellstein, German Mouse Clinic Consortium

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

17 Citations (Scopus)


Fibroblast growth factor-binding protein 1 (FGFBP1) is a secreted chaperone that mobilizes paracrine-acting FGFs, stored in the extracellular matrix, and presents them to their cognate receptors. FGFBP1 enhances FGF signaling including angiogenesis during cancer progression and is upregulated in various cancers. Here we evaluated the contribution of endogenous FGFBP1 to a wide range of organ functions as well as to skin pathologies using Fgfbp1-knockout mice. Relative to wild-type littermates, knockout mice showed no gross pathologies. Still, in knockout mice a significant thickening of the epidermis associated with a decreased transepidermal water loss and increased proinflammatory gene expression in the skin was detected. Also, skin carcinogen challenge by 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoyl-phorbol-13-acetate resulted in delayed and reduced papillomatosis in knockout mice. This was paralleled by delayed healing of skin wounds and reduced angiogenic sprouting in subcutaneous matrigel plugs. Heterozygous green fluorescent protein (GFP)–knock-in mice revealed rapid induction of gene expression during papilloma induction and during wound healing. Examination of wild-type skin grafted onto Fgfbp1 GFP–knock-in reporter hosts and bone marrow transplants from the GFP-reporter model into wild-type hosts revealed that circulating Fgfbp1-expressing cells migrate into healing wounds. We conclude that tissue-resident and circulating Fgfbp1-expressing cells modulate skin carcinogenesis and inflammation.

Original languageEnglish
Pages (from-to)179-188
Number of pages10
JournalJournal of Investigative Dermatology
Issue number1
Publication statusPublished - Jan 2018


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