SERPINE2, an inhibitor of plasminogen activators, is highly expressed in the human endometrium during the secretory phase

Abstract

Background: SERPINE2, also known as protease nexin-1, belongs to the serine protease inhibitor (SERPIN) superfamily. It is one of the potent SERPINs that modulates the activity of plasminogen activators (PAs). PAs and their SERPIN inhibitors, such as SERPINB2 and SERPINE1, were expressed in the human endometrium and were implicated in implantation. However, expression data about SERPINE2 in the human endometrium is still unknown. Thus, we conducted an investigation to reveal the spatiotemporal and cellular expression of SERPINE2 in the human uterus during the menstrual cycle. Methods: Seven patients who underwent a hysterectomy and samples of 120 archived patients' endometrial curettage or parts of the uterus that were formalin-fixed and embedded in paraffin. Western blotting was performed to evaluate the specificity and sensitivity of the antibody. Immunohistochemistry was conducted to localize the SERPINE2 expression site. Quantitative analysis was conducted to evaluate expression levels of SERPINE2 in various sub-phases of the menstrual cycle. Results: The SERPINE2 protein was primarily detected in the uterine fluid during the mid-and late-secretory phases of the menstrual cycle. It was predominantly expressed in the luminal and glandular epithelium, less in the myometrium, and only dispersedly in certain stromal cells throughout the menstrual cycle. A quantitative analysis of expression levels of SERPINE2 in the glandular epithelium revealed that it was highly expressed in the endometrium during the secretory phase compared to the proliferative phase. Conclusions: The SERPINE2 protein is highly expressed in the endometrium during the secretory phase, indicating that it may participate in tissue remodeling involved in implantation.

Expression pattern of human SERPINE2 in a variety of human tumors

“…2A and 4A), suggesting its extracellular function may associate with glandular secretion. Indeed, it has been reported that SERPINE2 was highly expressed in the endometrium during the secretory phase compared with the proliferative phase, indicating that it may participate in tissue remodeling during implantation in the placenta and uterus (31,32). A high SERPINE2 level was found in the inhibition of cumulus expansion and oocyte maturation (33).…”

SerpinE2 promotes multiple cell proliferation and drug resistance in osteosarcoma

“…Osteosarcoma, as one of the most dangerous malignant bone tumors, shows high propensity for invasion and proliferation. Recent studies have reported that SerpinE2 is highly expressed in different tumor tissues (12)(13)(14)16). The over-expression of SerpinE2 can promote tumor progression.…”

“…Serpins also exhibit a role as anti-plasminogen activators, which act as a shield for cancer from deleterious signals of astrocytes (9,10). Among these proteins, SerpinE2 is an extracellular plasminogen activator inhibitor and regulates broad key factors of tumor progression (11)(12)(13). In addition, SerpinE2 was found to be increased in pancreatic tumors (14), breast tumors (15), colorectal tumors (16) and oral squamous carcinomas (17).…”

Involvement of the Serine Protease Inhibitor, SERPINE2, and the Urokinase Plasminogen Activator in Cumulus Expansion and Oocyte Maturation

“…It is extensively expressed in reproductive tissues, e.g., the placenta [23], [24], uterus [24], [25], ovary [26], [27], and seminal vesicles [28]. In addition to its protease inhibitor role, SERPINE2 functions as a sperm decapacitation factor [29].…”