The expression pattern and functional role of REIC/Dkk-3 in the development of cutaneous squamous cell carcinoma. Issue 1 (October 2016) - Shin, Jung-Min
Highlights: ⿢ REIC/Dkk-3 is involved in the early development of squamous cell carcinoma. ⿢ REIC/Dkk-3 inhibited the formation of cutaneous squamous cell carcinoma in vivo test. ⿢ The anti-cancer effect of REIC/Dkk-3 may arise from suppression of tumorigenic cancer cells and the regulation of cell cycle. Abstract: Background: The exact physiological function of REIC/Dkk-3 in the development of squamous cell carcinoma(SCC) remains unclear. Objective: We aimed to investigate the expression pattern and functional role of REIC/Dkk-3 in the development of SCC. Methods: We stained normal skin, actinic keratosis (AK) and SCC tissue with REIC/Dkk-3. The proliferation and migration of SCC 12 over-expressed with REIC/Dkk-3 were observed. For in vivo study, SCC12 cells in PBS, SCC12 cells containing LacZ, and REIC/Dkk-3-transduced SCC 12 cells were injected intra-dermally into the left and right backside flanks of SCID mice respectively, and tumor growth was evaluated. Results: REIC/Dkk-3 staining was detected throughout the full epidermis in normal skin, focally positive in AK. Negative or very low stain of REIC/Dkk-3 was observed in SCC in situ, keratoacanthoma, and SCC. REIC/Dkk-3 mRNA level in SCC was very low compared with that in normal skin tissue. REIC/Dkk-3 significantly decreased the proliferation and migration of SCC12 cells comparing with control (p < 0.05). Cyclin D1 and CDK4/6 expression was slightly lower and p21 was very higher in REIC/Dkk-3-overexpressed group than in the LacZ group. Fewer ITGA6 cells were found in the REIC/Dkk-3 overexpressed group than in the LacZ control (p < 0.01). Mean tumor volume was smallest in the REIC/Dkk-3 overexpressed group (p < 0.01) 21 days after the intradermal injection of SCC12 cells. Conclusion: REIC/Dkk-3 could be involved early in SCC development and have inhibitory effect on the development of SCC.