Zhang Dongmei, Fu Mingjing, Li Lingyan, Ye Huan, Song Zhiqi, Piao Yongjun
Department of Physiology, Dalian Medical University, Dalian, China.
Department of Dermatology, The First Affiliated Hospital of Dalian Medical University, China.
Pathol Res Pract. 2017 Sep;213(9):1119-1124. doi: 10.1016/j.prp.2017.07.013. Epub 2017 Jul 14.
Protein kinase C delta (PKC-δ) has been identified as a tumor suppressor. However, the effects of PKC-δ on the cancer stem cells in squamous cell carcinomas (SCC) have not been clarified. The purpose of this study was to detect the regulation of PKC-δ on cancer stem cell among SSC cells and the role of p63 during the regulation. Immunohistochemistry of human cutaneous SCC tissues was performed to detect the expression of PKC-δ. After the human SCC13 cells infected by recombinant adenoviruses, the cell proliferation were determined. The correlation of PKC-δ and p63 was detected by western blot. The colony forming activity and the number of cancer stem cells (CSCs) in SCC identified by double-staining with anti-integrin α and anti-CD71 antibodies were detected. The expression of PKC-δ was obviously decreased in SCC tissues compared with that in normal skin tissues. The higher protein level of p63 in SCC was attenuated by the transfection of PKC-δ. The higher proliferation capacity of SCC13 cells, the higher activity and expression of CSCs in SCC13 cells induced by p63 were significantly suppressed by the transfection of PKC-δ. In conclusion, PKC-δ played as a protective role in SCC partly by down-regulating p63, leading to the suppression of SCC cell proliferation, attenuation of the activity and expression of CSCs in SCC cells.
蛋白激酶Cδ(PKC-δ)已被确定为一种肿瘤抑制因子。然而,PKC-δ对鳞状细胞癌(SCC)中癌症干细胞的影响尚未阐明。本研究的目的是检测PKC-δ对SSC细胞中癌症干细胞的调控作用以及p63在该调控过程中的作用。对人皮肤SCC组织进行免疫组织化学检测PKC-δ的表达。在用重组腺病毒感染人SCC13细胞后,测定细胞增殖情况。通过蛋白质印迹法检测PKC-δ与p63的相关性。检测用抗整合素α和抗CD71抗体双重染色鉴定的SCC中集落形成活性和癌症干细胞(CSC)数量。与正常皮肤组织相比,SCC组织中PKC-δ的表达明显降低。PKC-δ转染可减弱SCC中p63较高的蛋白水平。PKC-δ转染可显著抑制SCC13细胞较高的增殖能力、p63诱导的SCC13细胞中CSC的较高活性和表达。总之,PKC-δ在SCC中发挥保护作用,部分是通过下调p63,导致SCC细胞增殖受到抑制,SCC细胞中CSC的活性和表达减弱。