| First Author | Chang PL | Year | 2014 |
| Journal | J Dermatol Sci | Volume | 75 |
| Issue | 2 | Pages | 121-32 |
| PubMed ID | 24888687 | Mgi Jnum | J:316615 |
| Mgi Id | MGI:6839411 | Doi | 10.1016/j.jdermsci.2014.05.002 |
| Citation | Chang PL, et al. (2014) Osteopontin facilitates ultraviolet B-induced squamous cell carcinoma development. J Dermatol Sci 75(2):121-32 |
| abstractText | 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. |
