title: Procathepsin D secreted by HaCaT keratinocyte cells - A novel regulator of keratinocyte growth.
abstract: Procathepsin D (pCD), the precursor form of lysosomal aspartic protease, is overexpressed and secreted by various carcinomas. The fact that secreted pCD plays an essential role in progression of cancer has been established. In this study, we describe substantial secretion of pCD by the human keratinocyte cell line HaCaT, under serum-free conditions. Moreover, exogenous addition of purified pCD enhanced the proliferation of HaCaT cells. The proliferative effect of pCD was inhibited by a monoclonal antibody against the activation peptide (AP) of pCD. Treatment of HaCaT cells with pCD or AP led to the secretion of a set of cytokines that might promote the growth of cells in a paracrine manner. The role of secreted pCD and its mechanism of action were studied in a scratch wound model and the presence of pCD and AP enhanced regeneration, while this effect was reversed by the addition of anti-AP antibody. Expression and secretion of pCD was upregulated in HaCaT cells exposed to various stress conditions. Taken together, our results strongly suggest that the secretion of pCD is not only linked to cancer cells but also plays a role in normal physiological conditions like wound healing and tissue remodeling.
authors.affiliation: Department of Pathology, University of Louisville, 511 S. Floyd Street, MDR Building, Louisville, KY 40202, USA.
authors.forename: Aruna
authors.initials: A
authors.lastname: Vashishta
authors.forename: Sujata
authors.initials: S
authors.lastname: Saraswat Ohri
authors.forename: Jana
authors.initials: J
authors.lastname: Vetvickova
authors.forename: Martin
authors.initials: M
authors.lastname: Fusek
authors.forename: Jitka
authors.initials: J
authors.lastname: Ulrichova
authors.forename: Vaclav
authors.initials: V
authors.lastname: Vetvicka
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002402:Cathepsin D / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004792:Enzyme Precursors / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D018882:Heat Stress Disorders / Q000503:physiopathology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D012038:Regeneration / Q000502:physiology; D012878:Skin Neoplasms / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014945:Wound Healing / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D004792:Enzyme Precursors; C058345:procathepsin D; D002402:Cathepsin D