Promotion of the occurrence of endometrioid carcinoma by S100 calcium binding protein P.

ABSTRACT

BACKGROUND: Endometrial cancer, one of the most common malignant tumors, is a serious threat to women's health. Endometrial hyperplasia is a precursor of endometrial cancer. S100 calcium binding protein P (S100P) has been found to play important roles in many types of cancer. The present study aimed to investigate the expression of S100P in endometrial cancer and its precursor lesions, and to explore the possible mechanisms. METHODS: We collected paraffin sections of normal endometrium, simple and complex non-atypical hyperplasia, atypical hyperplasia, and endometrioid carcinoma. The expression of S100P in endometrial cancer and its precancerous lesions was observed using immunohistochemistry. We also cultured primary endometrial cells and endometrial cancer cell lines (Ishikawa and RL95-2), and observed the expression of S100P in these cells. Laser confocal microscopy was used to observe the co-localization of S100P and its interacting protein Ezrin in RL95-2 cells. We employed lentiviruses to knockdown and overexpress S100P and then detected the F-actin distribution and cell invasion using phalloidin staining and Transwell assays. RESULTS: There was a gradual increase in the S100P signal as the disease progressed from normal endometrium and simple non-atypical hyperplasia, to complex non-atypical hyperplasia, atypical hyperplasia, and then to endometrial cancer. S100P was mainly distributed in the cytoplasm and co-localized with Ezrin in endometrial cancer cells. After knocking down S100P, F-actin aggregated in the nucleus or to the local cell membrane. Furthermore, knockdown of S100P in Ishikawa cells decreased their cell invasion capability. Meanwhile, S100P overexpression in endometrial stromal cells increased cell invasion. CONCLUSIONS: These data suggested that S100P might be involved in the occurrence and development of endometrial cancer via interaction with Ezrin and re-organization of F-actin to promote cell invasion.