S100P expression in human esophageal epithelial cells: Human esophageal epithelial cells sequentially produce different S100 proteins in the process of differentiation

Abstract

Extracellular calcium ions (Ca(2+)) are important in regulating the differentiation of keratinocytes and squamous epithelial cells. To clarify the mechanisms involved in the differentiation of human esophageal epithelial cells (EECs), we used the primary culture of human EECs, which can be differentiated by increasing the concentration of extracellular Ca(2+), and tried to reveal the extracellular Ca(2+) inducible genes using a differential display (DD) method. We found that the calcium-binding protein S100P showed a Ca(2+)-inducible expression in the EECs. Our immunohistochemical study demonstrated that differentiated large EECs expressing S100P overlie immature proliferating cells which lack S100P immunoreactivity. S100P was detected in vivo in the suprabasal layers of the epithelium. These findings indicate that S100P expression is closely associated with differentiation of human EECs. We also investigated the expression of other S100 proteins, including S100A2, S100A6, and CAAF1 (S100A12), in human EECs. Most of the immature EECs were positive for S100A2 and S100A6, whereas the S100A12-producing cells were similar to the S100P-producing cells. In vivo, S100A12 was strongly detected on all epithelial cells except for basal and proliferating cells. S100A2 was detected on all of the epithelial cells. S100A6 was preferentially seen in the cells of basal layers. These findings suggest that within EECs S100 proteins might play important roles in cell differentiation during specific stages. Among them, S100P expression is unique in that this protein is transiently expressed during the early stage of differentiation.