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Journal of Histochemistry and Cytochemistry, Vol. 46, 437-448, April 1998, Copyright © 1998, The Histochemical Society, Inc.

ARTICLE

Human TIMP-3 Is Expressed During Fetal Development, Hair Growth Cycle, and Cancer Progression

Kristiina Airolaa,b, Matti Ahonend, Nina Johanssond, Päivi Heikkiläc, Juha Kereb, Veli-Matti Kähärid, and Ulpu K. Saarialho–Kerea,b
a Department of Dermatology, Helsinki University Central Hospital, Helsinki, Finland
b Departments of Medical Genetics, Haartman Institute, University of Helsinki, Helsinki, Finland
c Pathology, Haartman Institute, University of Helsinki, Helsinki, Finland
d Department of Dermatology, Turku University Central Hospital, and Department of Medical Biochemistry and Medicity Research Laboratory, University of Turku, Turku, Finland

Correspondence to: Ulpu K. Saarialho–Kere, Dept. of Dermatology, Helsinki U. Central Hospital, Meilahdentie 2, 00250 Helsinki, Finland.

We studied the expression and regulation of TIMP-3, a recently cloned member of the tissue inhibitor of the metalloproteinase family, during human fetal development and in various human tissues, with emphasis on epithelial structures. Expression of TIMP-3 mRNA was detected by in situ hybridization in developing bone, kidney, and various mesenchymal structures. At 16 weeks of gestation, ectoderm-derived cells of hair germs expressed TIMP-3 mRNA, and beginning from the twentieth week consistent expression was detected in epithelial outer root sheath cells of growing hair follicles. In normal adult human skin, expression of TIMP-3 mRNA was limited to hair follicles, starting at the early anagen (growing) phase and vanishing at the catagen (regressing) phase. TIMP-3 mRNA was not detected in benign hair follicle-derived tumors but was present in tumor cells of infiltrative basal cell carcinomas and in surrounding stromal cells in squamous cell carcinomas. Human primary keratinocytes in culture expressed TIMP-3 mRNAs, the levels of which were upregulated by transforming growth factor-ß (TGF-ß), whereas interleukin-1ß (IL-1ß) and tumor necrosis factor-{alpha} (TNF-{alpha}) had no effect. Our results suggest a role for TIMP-3 in connective tissue remodeling during fetal development, hair growth cycle, and cancer progression. (J Histochem Cytochem 46:437–447, 1998)

Key Words: carcinogenesis, extracellular matrix, hair, TGF-ß


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