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Chemical-Induced Skin Carcinogenesis Model Using Dimethylbenz[a]Anthracene and 12-O-Tetradecanoyl Phorbol-13-Acetate DMBA-TPA
Published on: December 19, 2019
Osteopontin facilitates ultraviolet B-induced squamous cell carcinoma development
Pi-Ling Chang1, Yu-Hua Hsieh2, Chao-Cheng Wang3
1Department 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.
Osteopontin (OPN) is crucial for skin cancer development. OPN-null mice showed no cSCC development after UVB exposure, indicating OPN promotes tumor growth by protecting cells from apoptosis.
Area of Science:
- Dermatology
- Oncology
- Molecular Biology
Background:
- Osteopontin (OPN) is a matricellular glycoprotein.
- OPN is highly expressed in cutaneous squamous cell carcinomas (cSCCs) and actinic keratoses.
- OPN is implicated in photocarcinogenesis.
Purpose of the Study:
- To investigate the role of Osteopontin (OPN) in the development of cutaneous squamous cell carcinomas (cSCCs).
- To elucidate the function of OPN in photocarcinogenesis.
Main Methods:
- Comparison of cSCC development in wild-type (WT) and OPN-null mice under UVB irradiation.
- Assessment of UVB-induced OPN expression using Western blot, ELISA, and RT-PCR.
- Analysis of epidermal hyperplasia, apoptosis (TUNEL assay), and expression of CD44 and FAK.
Main Results:
- OPN-null mice did not develop cSCCs, unlike WT mice, after 43 weeks of UVB exposure.
- OPN protected basal keratinocytes from UVB-induced apoptosis and suppressed apoptosis in OPN-null cSCC cells.
- OPN enhanced cell survival by increasing FAK phosphorylation and CD44 expression.
Conclusions:
- Chronic UVB-induced Osteopontin (OPN) expression promotes the survival of initiated basal keratinocytes.
- OPN plays a critical role in facilitating the development of cutaneous squamous cell carcinomas (cSCCs).
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