Decoy receptor 3 promotes cell adhesion and enhances endometriosis development

Abstract

Endometriosis is a multifactorial inflammatory disease with persistent activation of the nuclear factor-κB (NF-κB) signalling pathway. Aberrant adhesion of endometrium is the essential step in the progression of endometriosis, but the molecular mechanism of ectopic growth of endometrium is still unclear. Decoy receptor 3 (DcR3)/TNFRSF6B, a pleiotropic immunomodulator regulated by oestrogen, is able to activate focal adhesion kinase to promote cell adhesion. We found that DcR3 is upregulated in human ectopic endometrial cells via activation of the Akt-NF-κB signalling pathway, and its expression level correlates positively with that of the adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and homing cell adhesion molecule (HCAM; CD44). In a multivariate regression model, DcR3 expression level was the most significant parameter associated with endometriosis severity. Knockdown of DcR3 not only downregulated the expression of ICAM-1 and HCAM, but also reduced cell adhesion and migration. In vivo investigation further showed that DcR3 promoted the growth and spread of endometrium, whereas knockdown of DcR3 by lentivirus-delivered short hairpin RNA inhibited ectopic adhesion of endometrium and abrogated endometriosis progression. These observations are in support of DcR3 playing a critical role in the pathogenesis of endometriosis, and the inhibition of DcR3 expression being a promising approach for the treatment of endometriosis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Identification of Circular RNAs as a Novel Biomarker for Ovarian Endometriosis

“…For instance, decoy receptor 3 ( DcR3 )/ TNFRSF6B , a pleiotropic immunomodulator regulated by estrogen, promotes cell adhesion and enhances endometriosis development by activating focal adhesion kinase (FAK). [ 29 ] PGC-1α , highly expressed in ovarian endometrioma, promotes local estrogen biosynthesis by stimulating aromatase expression and activity. [ 30 ]…”

“…[ 38 ] Moreover, the evidence revealed that TNFRSF6B stimulated endometriosis development by activating FAK. [ 29 ]…”

Risks of female genital tract related cancers (gynecological cancers) or breast cancer in women with and without chronic kidney disease

“…In term of risk of EOC/TC, there are a lot factors relating to the risk of EOC/TC, including genetic background, parity, the use of oral pills, hysterectomy, endometriosis, and PID. [ 44 – 49 ] The diagnosis of EOC/TC is often difficult and always delayed, contributing to more than two-thirds of cases of EOC/TC diagnosed when the disease has progressed to stage III or IV and involves the peritoneal cavity or other organs. [ 50 – 52 ] To overcome the above-mentioned limitation, many researchers attempted to make an early diagnosis of EOC/TC and decrease the EOC/TC-related morbidity or mortality using the different kinds of strategies [ 53 – 57 ] ; however, results are relatively disappointing.…”

Adhesion in Physiological, Benign and Malignant Proliferative States of the Endometrium: Microenvironment and the Clinical Big Picture

“…The role of NF-kB mediation of cellular adhesion processes is also of interest in the context of cancer immunotherapy [ 139 ], although the mechanism by which pathological NF-kB activation occurs in malignant disease remains a subject of ongoing debate. The role of decoy receptor 3 (DcR3) has been proposed as a potential mechanism to promote cell adhesion in the development of endometriosis [ 140 ]. DcR3 has long been recognised as a method by which cancer cells may evade NK and cytotoxic T-cells via the inhibition of FasL-induced apoptosis [ 141 ].…”

“…DcR3 has long been recognised as a method by which cancer cells may evade NK and cytotoxic T-cells via the inhibition of FasL-induced apoptosis [ 141 ]. Tsai et al [ 140 ] noted an increased activation of the Akt-NF-kB signalling pathway in ectopic endometrium, with consequent upregulation of DcR3. In this xenograft study, DcR3 expression levels correlated both with ICAM-1 levels and with those of homing cell adhesion molecule (HCAM).…”