Format

Send to

Choose Destination
J Invest Dermatol. 2018 Jan;138(1):179-188. doi: 10.1016/j.jid.2017.07.847. Epub 2017 Aug 31.

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

Author information

1
Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA. Electronic address: mos6@georgetown.edu.
2
Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
3
Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA; Department of Chemistry, Purdue University System, West Lafayette, Indiana, USA.
4
Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA; Department of Medicine, Washington University in Saint Louis School of Medicine, Saint Louis, Missouri, USA.
5
Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA; Department of Chemistry, Thomas Jefferson High School for Science and Technology, Alexandria, Virginia, USA.
6
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
7
Department of Infection and Immunity, Luxembourg Institute of Health, Esch-sur-Alzette, Luxembourg; Department of Dermatology and Allergy Center, Odense Research Center for Anaphylaxis, University of Southern Denmark, Odense, Denmark.
8
Center of Allergy & Environment (ZAUM), Technische Universität München (TUM) and Helmholtz Zentrum, Munich, Germany; German Center for Lung Research (DZL), Gießen, Germany.
9
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany; Chair of Experimental Genetics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, München, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
10
Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA. Electronic address: anton.wellstein@georgetown.edu.

Abstract

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.

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center