Pi-Ling Chang1, Yu-Hua Hsieh2, Chao-Cheng Wang3, M Margaret Juliana4, Yuko Tsuruta3, Laura Timares3, Craig Elmets5, Kang-Jey Ho6. 1. Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA; Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA; Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA. Electronic address: plchang@uab.edu. 2. Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL, USA. 3. Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA. 4. Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA. 5. Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL, USA; Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA. 6. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA.
Abstract
BACKGROUND: Osteopontin (OPN) is a matricellular glycoprotein that is markedly expressed in cutaneous squamous cell carcinomas (cSCCs) and in actinic keratoses implicating its role in photocarcinogenesis. OBJECTIVE: To determine whether OPN facilitates the development of cSCC and its function. METHODS: cSCCs development was compared between wild-type (WT) and OPN-null mice subjected to UVB irradiation for 43 weeks. UVB-induced OPN expression was determined by Western blot, immunoprecipitation, ELISA, and semi-quantitative RT-PCR. Epidermal layer and TUNEL analyses assessed if OPN mediates UVB-induced epidermal hyperplasia or suppresses UVB-induced apoptosis of basal keratinocytes, respectively. In vitro experiments determined whether OPN enhances cell survival of UVB-induced apoptosis and its potential mechanisms. Immunohistochemical analyses of epidermis assessed the expression of CD44 and focal adhesion kinase (FAK), molecules that mediate OPN survival function. RESULTS: Compared to female WT mice, OPN-null mice did not develop cSCCs. UVB irradiation stimulated OPN protein expression in the dorsal skin by 11h and remains high at 24-48h. OPN did not mediate UVB-induced epidermal hyperplasia; instead, it protected basal keratinocytes from undergoing apoptosis upon UVB exposure. Likewise, the addition of OPN suppressed UVB-induced OPN-null cSCC cell apoptosis, the activation of caspase-9 activity, and increased phosphorylation of FAK at Y397. Furthermore, the expression of CD44 and FAK in WT mice epidermis was greater than that of OPN-null mice prior to and during early acute UVB exposure. CONCLUSION: These data support the hypothesis that chronic UVB-induced OPN expression protects the survival of initiated basal keratinocytes and, consequently, facilitates cSCC develop.
BACKGROUND:Osteopontin (OPN) is a matricellular glycoprotein that is markedly expressed in cutaneous squamous cell carcinomas (cSCCs) and in actinic keratoses implicating its role in photocarcinogenesis. OBJECTIVE: To determine whether OPN facilitates the development of cSCC and its function. METHODS: cSCCs development was compared between wild-type (WT) and OPN-null mice subjected to UVB irradiation for 43 weeks. UVB-induced OPN expression was determined by Western blot, immunoprecipitation, ELISA, and semi-quantitative RT-PCR. Epidermal layer and TUNEL analyses assessed if OPN mediates UVB-induced epidermal hyperplasia or suppresses UVB-induced apoptosis of basal keratinocytes, respectively. In vitro experiments determined whether OPN enhances cell survival of UVB-induced apoptosis and its potential mechanisms. Immunohistochemical analyses of epidermis assessed the expression of CD44 and focal adhesion kinase (FAK), molecules that mediate OPN survival function. RESULTS: Compared to female WT mice, OPN-null mice did not develop cSCCs. UVB irradiation stimulated OPN protein expression in the dorsal skin by 11h and remains high at 24-48h. OPN did not mediate UVB-induced epidermal hyperplasia; instead, it protected basal keratinocytes from undergoing apoptosis upon UVB exposure. Likewise, the addition of OPN suppressed UVB-induced OPN-null cSCC cell apoptosis, the activation of caspase-9 activity, and increased phosphorylation of FAK at Y397. Furthermore, the expression of CD44 and FAK in WT mice epidermis was greater than that of OPN-null mice prior to and during early acute UVB exposure. CONCLUSION: These data support the hypothesis that chronic UVB-induced OPN expression protects the survival of initiated basal keratinocytes and, consequently, facilitates cSCC develop.
Authors: Hanna Siiskonen; Kari Törrönen; Timo Kumlin; Kirsi Rilla; Markku I Tammi; Raija H Tammi Journal: J Histochem Cytochem Date: 2011-08-10 Impact factor: 2.479
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Authors: Chu-Fang Chou; Yu-Hua Hsieh; Clinton J Grubbs; Venkatram R Atigadda; James A Mobley; Reinhard Dummer; Donald D Muccio; Isao Eto; Craig A Elmets; W Timothy Garvey; Pi-Ling Chang Journal: J Dermatol Sci Date: 2018-03-15 Impact factor: 4.563
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